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SAN DIEGO — Final results of the phase 3 Andromeda study confirmed that adding daratumumab (DARA) — a human CD38-targeting monoclonal antibody — to bortezomib, cyclophosphamide, and dexamethasone (VCd) improves outcomes in patients with newly diagnosed amyloid light chain (AL) amyloidosis.

Adding DARA to VCd (D-VCd; Darzalex Faspro; Janssen Biotech) provided deeper and more rapid hematologic response and clinically meaningful and statistically significant improvement in overall survival (OS) and major organ deterioration progression-free survival (MOD-PFS), combined with 40.7% cardiac complete response (CR), first author Efstathios Kastritis, MD, said during presentation of an oral abstract at the American Society of Hematology (ASH) 2024 Annual Meeting.

“The Andromeda study is the first comparing two contemporary regimens that shows a significant survival improvement for patients with AL amyloidosis,” said Kastritis, an associate professor at the National and Kapodistrian University of Athens in Greece. “These findings reaffirm frontline D-VCd as the standard of care in this difficult-to-treat disease.”

The regimen was approved for this indication in 2021 based on prior earlier findings from the Andromeda trial. The current results are from a preplanned analysis for MOD-PFS and OS.

At a median follow-up of 61.4 months, the overall hematologic CR rates were 59.5% and 19.2% among 388 patients randomized to receive D-VCd or VCd, respectively (odds ratio, 6.03), which showed continued improvement with additional DARA vs the 53.3% and 18.1% rates observed at the primary analysis, Kastritis reported.

Time to hematologic CR was 67.5 days and 85.0 days in the treatment groups, respectively, and median duration of hematologic CR was not reached in either group.

A significant 56% improvement was also observed in MOD-PFS (hazard ratio [HR], 0.44). Median MOD-PFS was not reached in the D-VCd group and was 30.3 months in the VCd group.

A significant 38% improvement was observed in OS (HR, 0.62), 5-year OS was 76.1% vs 64.7% in the D-VCd and VCd groups, respectively, he said.

“[The OS] benefit occurred even though more than 70% of the patients in the VCd arm who received a subsequent therapy were treated with a DARA-based regimen,” he stressed. “This further emphasizes the importance of using DSTS in the frontline setting.”

Trial participants had newly diagnosed AL amyloidosis with measurable hematologic disease, one or more involved organs, cardiac stage I-IIIA, estimated glomerular filtration rate of at least 20 mL/min, and absence of symptomatic multiple myeloma. They were randomized 1:1 to the two treatment groups. All patients received 1.3 mg/m2 of bortezomib by weekly injection, 300 mg/m2 of cyclophosphamide either by weekly oral or intravenous administration, and 20-40 mg of dexamethasone by weekly oral or intravenous administration for six 28-day cycles.

Those in the D-VCd group also received 1800 mg of DARA coformulated with rHuPH20 as a weekly injection in cycles 1-2, as a biweekly injection in cycles 3-6, and by injection every 4 weeks thereafter for up to 24 28-day cycles.

The median duration of treatment was 21.3 months for D-VCd and 5.3 months for VCd, and of 122 patients who received subsequent therapy, 82 (67%) received subsequent DARA.

Patients who achieved hematologic CR had better MOD-PFS and OS (HR, 0.30 and 0.41, respectively), regardless of the treatment received, he noted, adding that “this further supports that complete hematologic response is a valid early endpoint for the evaluation of anti-monoclonal therapies in AL amyloidosis.”

“I think this is very important for the further development of new treatments in this disease,” he said.

Of note, cardiac and renal response rates in the D-VCd group were about two to three times greater than those in the VCd group at 6, 12, 24, 36, and 48 months, Kastritis said.

Among 235 patients with an evaluable cardiac response, 113 achieved a very good partial response or better, including 76 of 118 (64.4%) in the D-VCd group and 37 of 117 (31.6%) in the VCd group. Of these, 48 (40.7%) and 16 (13.7%) achieved a cardiac CR.

Grade 3 or 4 treatment-emergent adverse events (TEAEs) occurring in at least 5% of patients in the D-VCd and VCd groups, respectively, were lymphopenia (13% and 10%), pneumonia (8% and 4%), hypokalemia (2% and 5%), and peripheral edema (3% and 6%), he noted, adding that systemic administration-related reactions occurred in 14 (7%) of patients receiving D-VCd; all were grade 1 or 2 and most (86%) occurred after the first injection. TEAEs led to treatment discontinuation in 5% and 4% of patients in the groups, respectively.

No new safety signals were observed during the extended follow-up, he said.

Kastritis reported relationships with Pfizer, Genesis Pharma, Sanofi, AbbVie, GSK, Prothena, Janssen, and Amgen.

A version of this article first appeared on Medscape.com.

SAN DIEGO — Final results of the phase 3 Andromeda study confirmed that adding daratumumab (DARA) — a human CD38-targeting monoclonal antibody — to bortezomib, cyclophosphamide, and dexamethasone (VCd) improves outcomes in patients with newly diagnosed amyloid light chain (AL) amyloidosis.

Adding DARA to VCd (D-VCd; Darzalex Faspro; Janssen Biotech) provided deeper and more rapid hematologic response and clinically meaningful and statistically significant improvement in overall survival (OS) and major organ deterioration progression-free survival (MOD-PFS), combined with 40.7% cardiac complete response (CR), first author Efstathios Kastritis, MD, said during presentation of an oral abstract at the American Society of Hematology (ASH) 2024 Annual Meeting.

“The Andromeda study is the first comparing two contemporary regimens that shows a significant survival improvement for patients with AL amyloidosis,” said Kastritis, an associate professor at the National and Kapodistrian University of Athens in Greece. “These findings reaffirm frontline D-VCd as the standard of care in this difficult-to-treat disease.”

The regimen was approved for this indication in 2021 based on prior earlier findings from the Andromeda trial. The current results are from a preplanned analysis for MOD-PFS and OS.

At a median follow-up of 61.4 months, the overall hematologic CR rates were 59.5% and 19.2% among 388 patients randomized to receive D-VCd or VCd, respectively (odds ratio, 6.03), which showed continued improvement with additional DARA vs the 53.3% and 18.1% rates observed at the primary analysis, Kastritis reported.

Time to hematologic CR was 67.5 days and 85.0 days in the treatment groups, respectively, and median duration of hematologic CR was not reached in either group.

A significant 56% improvement was also observed in MOD-PFS (hazard ratio [HR], 0.44). Median MOD-PFS was not reached in the D-VCd group and was 30.3 months in the VCd group.

A significant 38% improvement was observed in OS (HR, 0.62), 5-year OS was 76.1% vs 64.7% in the D-VCd and VCd groups, respectively, he said.

“[The OS] benefit occurred even though more than 70% of the patients in the VCd arm who received a subsequent therapy were treated with a DARA-based regimen,” he stressed. “This further emphasizes the importance of using DSTS in the frontline setting.”

Trial participants had newly diagnosed AL amyloidosis with measurable hematologic disease, one or more involved organs, cardiac stage I-IIIA, estimated glomerular filtration rate of at least 20 mL/min, and absence of symptomatic multiple myeloma. They were randomized 1:1 to the two treatment groups. All patients received 1.3 mg/m2 of bortezomib by weekly injection, 300 mg/m2 of cyclophosphamide either by weekly oral or intravenous administration, and 20-40 mg of dexamethasone by weekly oral or intravenous administration for six 28-day cycles.

Those in the D-VCd group also received 1800 mg of DARA coformulated with rHuPH20 as a weekly injection in cycles 1-2, as a biweekly injection in cycles 3-6, and by injection every 4 weeks thereafter for up to 24 28-day cycles.

The median duration of treatment was 21.3 months for D-VCd and 5.3 months for VCd, and of 122 patients who received subsequent therapy, 82 (67%) received subsequent DARA.

Patients who achieved hematologic CR had better MOD-PFS and OS (HR, 0.30 and 0.41, respectively), regardless of the treatment received, he noted, adding that “this further supports that complete hematologic response is a valid early endpoint for the evaluation of anti-monoclonal therapies in AL amyloidosis.”

“I think this is very important for the further development of new treatments in this disease,” he said.

Of note, cardiac and renal response rates in the D-VCd group were about two to three times greater than those in the VCd group at 6, 12, 24, 36, and 48 months, Kastritis said.

Among 235 patients with an evaluable cardiac response, 113 achieved a very good partial response or better, including 76 of 118 (64.4%) in the D-VCd group and 37 of 117 (31.6%) in the VCd group. Of these, 48 (40.7%) and 16 (13.7%) achieved a cardiac CR.

Grade 3 or 4 treatment-emergent adverse events (TEAEs) occurring in at least 5% of patients in the D-VCd and VCd groups, respectively, were lymphopenia (13% and 10%), pneumonia (8% and 4%), hypokalemia (2% and 5%), and peripheral edema (3% and 6%), he noted, adding that systemic administration-related reactions occurred in 14 (7%) of patients receiving D-VCd; all were grade 1 or 2 and most (86%) occurred after the first injection. TEAEs led to treatment discontinuation in 5% and 4% of patients in the groups, respectively.

No new safety signals were observed during the extended follow-up, he said.

Kastritis reported relationships with Pfizer, Genesis Pharma, Sanofi, AbbVie, GSK, Prothena, Janssen, and Amgen.

A version of this article first appeared on Medscape.com.

SAN DIEGO — Final results of the phase 3 Andromeda study confirmed that adding daratumumab (DARA) — a human CD38-targeting monoclonal antibody — to bortezomib, cyclophosphamide, and dexamethasone (VCd) improves outcomes in patients with newly diagnosed amyloid light chain (AL) amyloidosis.

Adding DARA to VCd (D-VCd; Darzalex Faspro; Janssen Biotech) provided deeper and more rapid hematologic response and clinically meaningful and statistically significant improvement in overall survival (OS) and major organ deterioration progression-free survival (MOD-PFS), combined with 40.7% cardiac complete response (CR), first author Efstathios Kastritis, MD, said during presentation of an oral abstract at the American Society of Hematology (ASH) 2024 Annual Meeting.

“The Andromeda study is the first comparing two contemporary regimens that shows a significant survival improvement for patients with AL amyloidosis,” said Kastritis, an associate professor at the National and Kapodistrian University of Athens in Greece. “These findings reaffirm frontline D-VCd as the standard of care in this difficult-to-treat disease.”

The regimen was approved for this indication in 2021 based on prior earlier findings from the Andromeda trial. The current results are from a preplanned analysis for MOD-PFS and OS.

At a median follow-up of 61.4 months, the overall hematologic CR rates were 59.5% and 19.2% among 388 patients randomized to receive D-VCd or VCd, respectively (odds ratio, 6.03), which showed continued improvement with additional DARA vs the 53.3% and 18.1% rates observed at the primary analysis, Kastritis reported.

Time to hematologic CR was 67.5 days and 85.0 days in the treatment groups, respectively, and median duration of hematologic CR was not reached in either group.

A significant 56% improvement was also observed in MOD-PFS (hazard ratio [HR], 0.44). Median MOD-PFS was not reached in the D-VCd group and was 30.3 months in the VCd group.

A significant 38% improvement was observed in OS (HR, 0.62), 5-year OS was 76.1% vs 64.7% in the D-VCd and VCd groups, respectively, he said.

“[The OS] benefit occurred even though more than 70% of the patients in the VCd arm who received a subsequent therapy were treated with a DARA-based regimen,” he stressed. “This further emphasizes the importance of using DSTS in the frontline setting.”

Trial participants had newly diagnosed AL amyloidosis with measurable hematologic disease, one or more involved organs, cardiac stage I-IIIA, estimated glomerular filtration rate of at least 20 mL/min, and absence of symptomatic multiple myeloma. They were randomized 1:1 to the two treatment groups. All patients received 1.3 mg/m2 of bortezomib by weekly injection, 300 mg/m2 of cyclophosphamide either by weekly oral or intravenous administration, and 20-40 mg of dexamethasone by weekly oral or intravenous administration for six 28-day cycles.

Those in the D-VCd group also received 1800 mg of DARA coformulated with rHuPH20 as a weekly injection in cycles 1-2, as a biweekly injection in cycles 3-6, and by injection every 4 weeks thereafter for up to 24 28-day cycles.

The median duration of treatment was 21.3 months for D-VCd and 5.3 months for VCd, and of 122 patients who received subsequent therapy, 82 (67%) received subsequent DARA.

Patients who achieved hematologic CR had better MOD-PFS and OS (HR, 0.30 and 0.41, respectively), regardless of the treatment received, he noted, adding that “this further supports that complete hematologic response is a valid early endpoint for the evaluation of anti-monoclonal therapies in AL amyloidosis.”

“I think this is very important for the further development of new treatments in this disease,” he said.

Of note, cardiac and renal response rates in the D-VCd group were about two to three times greater than those in the VCd group at 6, 12, 24, 36, and 48 months, Kastritis said.

Among 235 patients with an evaluable cardiac response, 113 achieved a very good partial response or better, including 76 of 118 (64.4%) in the D-VCd group and 37 of 117 (31.6%) in the VCd group. Of these, 48 (40.7%) and 16 (13.7%) achieved a cardiac CR.

Grade 3 or 4 treatment-emergent adverse events (TEAEs) occurring in at least 5% of patients in the D-VCd and VCd groups, respectively, were lymphopenia (13% and 10%), pneumonia (8% and 4%), hypokalemia (2% and 5%), and peripheral edema (3% and 6%), he noted, adding that systemic administration-related reactions occurred in 14 (7%) of patients receiving D-VCd; all were grade 1 or 2 and most (86%) occurred after the first injection. TEAEs led to treatment discontinuation in 5% and 4% of patients in the groups, respectively.

No new safety signals were observed during the extended follow-up, he said.

Kastritis reported relationships with Pfizer, Genesis Pharma, Sanofi, AbbVie, GSK, Prothena, Janssen, and Amgen.

A version of this article first appeared on Medscape.com.

Children with newly diagnosed immune thrombocytopenia (ITP) treated with eltrombopag as a frontline therapy show significantly improved platelet responses and other outcomes compared with the standard of care.

“This is the first time in 30 years that a new drug is being tested for newly diagnosed pediatric ITP,” said the study’s lead author, Kristin A. Shimano, MD, professor of pediatrics at the Benioff Children’s Hospital, University of California San Francisco, in a press statement for the study, presented at the American Society of Hematology (ASH) 2024 Annual Meeting earlier this month.

“We really think that this has the potential to transform the approach to the management of ITP in the newly diagnosed phase with the use of a therapy that can provide sustained hemostatic platelet counts to bridge the time that patients are at risk of bleeding events with the goal to wean off the medication for patients who have a natural resolution of their disease,” Shimano said in her talk.

While children with ITP, a rare autoimmune blood disorder, very often improve without the need for any treatment, some do require intervention, and the condition can become chronic. First-line therapies for those patients commonly include corticosteroids, intravenous immunoglobulin (IVIg), and anti-D globulin; however, side effects can be undesirable, and with their efficacy often temporary, patients can require monitoring and juggling of treatments.

Eltrombopag, an oral, daily thrombopoietin receptor agonist, was approved by the US Food and Drug Administration for children and adults with chronic ITP in 2015; however, research has been lacking on the benefits of the therapy for newly diagnosed pediatric patients.

To investigate the drug’s efficacy at that stage, Shimano and colleagues with the ITP Consortium of North America launched the prospective, open-label Pediatric ITP Newly diagnosed pts Epag vs Standard therapy (PINES) trial, enrolling 118 patients at 23 institutions between May 2019 and January 2024.

All enrollees had been diagnosed with ITP within 3 months and had been determined by their treating hematologist to require pharmacologic treatment.

Of the patients, about 40% were untreated, and 60% had been treated with at least one medication prior to the trial but did not have a lasting response.

The patients were stratified by age and prior treatment and randomized 2:1 to receive either eltrombopag (n = 78) or the investigator’s choice of one of three standard first-line therapies, including prednisone, IVIg, or anti-D globulin at specified doses (n = 40). Overall, 29 in the standard-of-care arm received prednisone and 11 received IVIg. The patients had a median age of 8 years.

For the study’s primary endpoint, patients in the eltrombopag group had a significantly greater sustained response at 12 weeks, defined as having at least three of four platelet counts > 50 × 109/L during weeks 6-12 without the need for rescue treatment, with a rate of 63% vs 35% in the standard-of-care group (P = .0054).

There were no significant differences between the two groups in terms of the proportion of patients with a high bleeding score at weeks 1-4 and week 12.

However, those in the eltrombopag arm had a significantly lower rate of receiving rescue therapy (18% vs 38% with the standard of care; P = .02).

Both groups showed clinically meaningful improvements from baseline in terms of health-related quality of life, as assessed by parent proxy-reported KIT overall scores.

Twenty adverse events that were grade 3 or higher, including six serious adverse events, occurred in each of the study’s arms, with the most common events including headache and epistaxis.

Treatment-related serious adverse events occurred among six patients in the eltrombopag group and one in the control group, but importantly, no thromboembolic events were reported.

One intracranial hemorrhage occurred in the eltrombopag arm.

With eltrombopag having a slower effect than some other treatments, Shimano cautioned that the therapy is not recommended for patients with severe bleeding.

“Patients with grade 4 or 5 bleeding at the time of screening were specifically excluded from the study, so for patients who have very severe bleeding who need to get their platelets up very quickly, this would not be the ideal therapy for them,” she noted.

On the basis of results, the trial was recommended to close early due to efficacy; however, the participants are being followed for a total of 12 months to determine the durability of the responses, including in terms of bleeding events, quality of life, or the development of chronic ITP.

“We have shown that in pediatric patients with newly diagnosed ITP requiring pharmacologic treatment, eltrombopag resulted in a significant, clinically relevant higher rate of a durable platelet response in the absence of rescue treatment as compared with standard first-line therapies,” Shimano said.

“Eltrombopag could certainly be added to the medication choices hematologists consider as they are making treatment decisions with families, and it is an option that could potentially raise platelets for a more sustained period in children with ITP in the newly diagnosed period, which is one of the most difficult times for patients with regard to the impact of the disease on bleeding symptoms and quality of life,” she added.

Commenting on the study, James B. Bussel, MD, emeritus professor of pediatrics, medicine and obstetrics and gynecology at Weill Cornell Medicine in New York City, commented that “generally, a short-term increase in platelets is the biggest challenge, which is getting the patient to the point of not requiring future treatment to get better.”

“If more children can be shown to be going into remission earlier, that would be great,” he said.

While eltrombopag is known to be effective in chronic ITP, a key caveat of its use in newly diagnosed patients is the question of whether patients will get better on their own and feasibly be able to be spared the cost and burden of treatment in the first place.

However, identifying which patients will fit that profile isn’t always easy.

“Exactly which child needs treatment can be hard to determine, and there is some debate about that,” Bussel noted.

“The theoretic standard is that the platelet count doesn’t matter — only whether the patient is bleeding a lot, and then there is debate over treatment based on bleeding scores,” he said.

Quality-of-life issues, such as patients’ ability to take part in activities, are also a key consideration.

“It would be great if eltrombopag can support children who really need it and provide clear unequivocal benefit beyond just increasing the platelet count, but also leading to better quality of life,” Bussel said.

The new findings are “a very encouraging start, but I’d really like to see what the story is at 1 year.”

The study was funded by Novartis, maker of eltrombopag, and sponsored by the ITP Consortium of North America. Shimano disclosed ties with Sanofi, Sobi, Daiichi Sankyo, Novartis, and Pfizer. Bussel reported a relationship with Novartis that ended more than 2 years ago.

A version of this article first appeared on Medscape.com.

Children with newly diagnosed immune thrombocytopenia (ITP) treated with eltrombopag as a frontline therapy show significantly improved platelet responses and other outcomes compared with the standard of care.

“This is the first time in 30 years that a new drug is being tested for newly diagnosed pediatric ITP,” said the study’s lead author, Kristin A. Shimano, MD, professor of pediatrics at the Benioff Children’s Hospital, University of California San Francisco, in a press statement for the study, presented at the American Society of Hematology (ASH) 2024 Annual Meeting earlier this month.

“We really think that this has the potential to transform the approach to the management of ITP in the newly diagnosed phase with the use of a therapy that can provide sustained hemostatic platelet counts to bridge the time that patients are at risk of bleeding events with the goal to wean off the medication for patients who have a natural resolution of their disease,” Shimano said in her talk.

While children with ITP, a rare autoimmune blood disorder, very often improve without the need for any treatment, some do require intervention, and the condition can become chronic. First-line therapies for those patients commonly include corticosteroids, intravenous immunoglobulin (IVIg), and anti-D globulin; however, side effects can be undesirable, and with their efficacy often temporary, patients can require monitoring and juggling of treatments.

Eltrombopag, an oral, daily thrombopoietin receptor agonist, was approved by the US Food and Drug Administration for children and adults with chronic ITP in 2015; however, research has been lacking on the benefits of the therapy for newly diagnosed pediatric patients.

To investigate the drug’s efficacy at that stage, Shimano and colleagues with the ITP Consortium of North America launched the prospective, open-label Pediatric ITP Newly diagnosed pts Epag vs Standard therapy (PINES) trial, enrolling 118 patients at 23 institutions between May 2019 and January 2024.

All enrollees had been diagnosed with ITP within 3 months and had been determined by their treating hematologist to require pharmacologic treatment.

Of the patients, about 40% were untreated, and 60% had been treated with at least one medication prior to the trial but did not have a lasting response.

The patients were stratified by age and prior treatment and randomized 2:1 to receive either eltrombopag (n = 78) or the investigator’s choice of one of three standard first-line therapies, including prednisone, IVIg, or anti-D globulin at specified doses (n = 40). Overall, 29 in the standard-of-care arm received prednisone and 11 received IVIg. The patients had a median age of 8 years.

For the study’s primary endpoint, patients in the eltrombopag group had a significantly greater sustained response at 12 weeks, defined as having at least three of four platelet counts > 50 × 109/L during weeks 6-12 without the need for rescue treatment, with a rate of 63% vs 35% in the standard-of-care group (P = .0054).

There were no significant differences between the two groups in terms of the proportion of patients with a high bleeding score at weeks 1-4 and week 12.

However, those in the eltrombopag arm had a significantly lower rate of receiving rescue therapy (18% vs 38% with the standard of care; P = .02).

Both groups showed clinically meaningful improvements from baseline in terms of health-related quality of life, as assessed by parent proxy-reported KIT overall scores.

Twenty adverse events that were grade 3 or higher, including six serious adverse events, occurred in each of the study’s arms, with the most common events including headache and epistaxis.

Treatment-related serious adverse events occurred among six patients in the eltrombopag group and one in the control group, but importantly, no thromboembolic events were reported.

One intracranial hemorrhage occurred in the eltrombopag arm.

With eltrombopag having a slower effect than some other treatments, Shimano cautioned that the therapy is not recommended for patients with severe bleeding.

“Patients with grade 4 or 5 bleeding at the time of screening were specifically excluded from the study, so for patients who have very severe bleeding who need to get their platelets up very quickly, this would not be the ideal therapy for them,” she noted.

On the basis of results, the trial was recommended to close early due to efficacy; however, the participants are being followed for a total of 12 months to determine the durability of the responses, including in terms of bleeding events, quality of life, or the development of chronic ITP.

“We have shown that in pediatric patients with newly diagnosed ITP requiring pharmacologic treatment, eltrombopag resulted in a significant, clinically relevant higher rate of a durable platelet response in the absence of rescue treatment as compared with standard first-line therapies,” Shimano said.

“Eltrombopag could certainly be added to the medication choices hematologists consider as they are making treatment decisions with families, and it is an option that could potentially raise platelets for a more sustained period in children with ITP in the newly diagnosed period, which is one of the most difficult times for patients with regard to the impact of the disease on bleeding symptoms and quality of life,” she added.

Commenting on the study, James B. Bussel, MD, emeritus professor of pediatrics, medicine and obstetrics and gynecology at Weill Cornell Medicine in New York City, commented that “generally, a short-term increase in platelets is the biggest challenge, which is getting the patient to the point of not requiring future treatment to get better.”

“If more children can be shown to be going into remission earlier, that would be great,” he said.

While eltrombopag is known to be effective in chronic ITP, a key caveat of its use in newly diagnosed patients is the question of whether patients will get better on their own and feasibly be able to be spared the cost and burden of treatment in the first place.

However, identifying which patients will fit that profile isn’t always easy.

“Exactly which child needs treatment can be hard to determine, and there is some debate about that,” Bussel noted.

“The theoretic standard is that the platelet count doesn’t matter — only whether the patient is bleeding a lot, and then there is debate over treatment based on bleeding scores,” he said.

Quality-of-life issues, such as patients’ ability to take part in activities, are also a key consideration.

“It would be great if eltrombopag can support children who really need it and provide clear unequivocal benefit beyond just increasing the platelet count, but also leading to better quality of life,” Bussel said.

The new findings are “a very encouraging start, but I’d really like to see what the story is at 1 year.”

The study was funded by Novartis, maker of eltrombopag, and sponsored by the ITP Consortium of North America. Shimano disclosed ties with Sanofi, Sobi, Daiichi Sankyo, Novartis, and Pfizer. Bussel reported a relationship with Novartis that ended more than 2 years ago.

A version of this article first appeared on Medscape.com.

Children with newly diagnosed immune thrombocytopenia (ITP) treated with eltrombopag as a frontline therapy show significantly improved platelet responses and other outcomes compared with the standard of care.

“This is the first time in 30 years that a new drug is being tested for newly diagnosed pediatric ITP,” said the study’s lead author, Kristin A. Shimano, MD, professor of pediatrics at the Benioff Children’s Hospital, University of California San Francisco, in a press statement for the study, presented at the American Society of Hematology (ASH) 2024 Annual Meeting earlier this month.

“We really think that this has the potential to transform the approach to the management of ITP in the newly diagnosed phase with the use of a therapy that can provide sustained hemostatic platelet counts to bridge the time that patients are at risk of bleeding events with the goal to wean off the medication for patients who have a natural resolution of their disease,” Shimano said in her talk.

While children with ITP, a rare autoimmune blood disorder, very often improve without the need for any treatment, some do require intervention, and the condition can become chronic. First-line therapies for those patients commonly include corticosteroids, intravenous immunoglobulin (IVIg), and anti-D globulin; however, side effects can be undesirable, and with their efficacy often temporary, patients can require monitoring and juggling of treatments.

Eltrombopag, an oral, daily thrombopoietin receptor agonist, was approved by the US Food and Drug Administration for children and adults with chronic ITP in 2015; however, research has been lacking on the benefits of the therapy for newly diagnosed pediatric patients.

To investigate the drug’s efficacy at that stage, Shimano and colleagues with the ITP Consortium of North America launched the prospective, open-label Pediatric ITP Newly diagnosed pts Epag vs Standard therapy (PINES) trial, enrolling 118 patients at 23 institutions between May 2019 and January 2024.

All enrollees had been diagnosed with ITP within 3 months and had been determined by their treating hematologist to require pharmacologic treatment.

Of the patients, about 40% were untreated, and 60% had been treated with at least one medication prior to the trial but did not have a lasting response.

The patients were stratified by age and prior treatment and randomized 2:1 to receive either eltrombopag (n = 78) or the investigator’s choice of one of three standard first-line therapies, including prednisone, IVIg, or anti-D globulin at specified doses (n = 40). Overall, 29 in the standard-of-care arm received prednisone and 11 received IVIg. The patients had a median age of 8 years.

For the study’s primary endpoint, patients in the eltrombopag group had a significantly greater sustained response at 12 weeks, defined as having at least three of four platelet counts > 50 × 109/L during weeks 6-12 without the need for rescue treatment, with a rate of 63% vs 35% in the standard-of-care group (P = .0054).

There were no significant differences between the two groups in terms of the proportion of patients with a high bleeding score at weeks 1-4 and week 12.

However, those in the eltrombopag arm had a significantly lower rate of receiving rescue therapy (18% vs 38% with the standard of care; P = .02).

Both groups showed clinically meaningful improvements from baseline in terms of health-related quality of life, as assessed by parent proxy-reported KIT overall scores.

Twenty adverse events that were grade 3 or higher, including six serious adverse events, occurred in each of the study’s arms, with the most common events including headache and epistaxis.

Treatment-related serious adverse events occurred among six patients in the eltrombopag group and one in the control group, but importantly, no thromboembolic events were reported.

One intracranial hemorrhage occurred in the eltrombopag arm.

With eltrombopag having a slower effect than some other treatments, Shimano cautioned that the therapy is not recommended for patients with severe bleeding.

“Patients with grade 4 or 5 bleeding at the time of screening were specifically excluded from the study, so for patients who have very severe bleeding who need to get their platelets up very quickly, this would not be the ideal therapy for them,” she noted.

On the basis of results, the trial was recommended to close early due to efficacy; however, the participants are being followed for a total of 12 months to determine the durability of the responses, including in terms of bleeding events, quality of life, or the development of chronic ITP.

“We have shown that in pediatric patients with newly diagnosed ITP requiring pharmacologic treatment, eltrombopag resulted in a significant, clinically relevant higher rate of a durable platelet response in the absence of rescue treatment as compared with standard first-line therapies,” Shimano said.

“Eltrombopag could certainly be added to the medication choices hematologists consider as they are making treatment decisions with families, and it is an option that could potentially raise platelets for a more sustained period in children with ITP in the newly diagnosed period, which is one of the most difficult times for patients with regard to the impact of the disease on bleeding symptoms and quality of life,” she added.

Commenting on the study, James B. Bussel, MD, emeritus professor of pediatrics, medicine and obstetrics and gynecology at Weill Cornell Medicine in New York City, commented that “generally, a short-term increase in platelets is the biggest challenge, which is getting the patient to the point of not requiring future treatment to get better.”

“If more children can be shown to be going into remission earlier, that would be great,” he said.

While eltrombopag is known to be effective in chronic ITP, a key caveat of its use in newly diagnosed patients is the question of whether patients will get better on their own and feasibly be able to be spared the cost and burden of treatment in the first place.

However, identifying which patients will fit that profile isn’t always easy.

“Exactly which child needs treatment can be hard to determine, and there is some debate about that,” Bussel noted.

“The theoretic standard is that the platelet count doesn’t matter — only whether the patient is bleeding a lot, and then there is debate over treatment based on bleeding scores,” he said.

Quality-of-life issues, such as patients’ ability to take part in activities, are also a key consideration.

“It would be great if eltrombopag can support children who really need it and provide clear unequivocal benefit beyond just increasing the platelet count, but also leading to better quality of life,” Bussel said.

The new findings are “a very encouraging start, but I’d really like to see what the story is at 1 year.”

The study was funded by Novartis, maker of eltrombopag, and sponsored by the ITP Consortium of North America. Shimano disclosed ties with Sanofi, Sobi, Daiichi Sankyo, Novartis, and Pfizer. Bussel reported a relationship with Novartis that ended more than 2 years ago.

A version of this article first appeared on Medscape.com.

TOPLINE:

Adding camrelizumab to neoadjuvant chemotherapy increases pathological complete response rate to 56.8% vs 44.7% with placebo in early or locally advanced triple-negative breast cancer. The combination shows consistent benefits across patient subgroups with a manageable safety profile.

METHODOLOGY:

• A randomized, double-blind, phase 3 trial enrolled 441 females (median age, 48 years) with early or locally advanced triple-negative breast cancer from 40 hospitals in China between November 2020 and May 2023.
• Participants were randomized 1:1 to receive either camrelizumab 200 mg (n = 222) or placebo (n = 219) combined with chemotherapy every 2 weeks, with median follow-up period of 14.4 months.
• Treatment included nab-paclitaxel (100 mg/m²) plus carboplatin (area under curve, 1.5) on days 1, 8, and 15 in 28-day cycles for 16 weeks, followed by epirubicin (90 mg/m²) and cyclophosphamide (500 mg/m²) every 2 weeks for 8 weeks.
• The primary endpoint was pathological complete response, defined as no invasive tumor in breast and lymph nodes.

TAKEAWAY:

• Pathological complete response was achieved in 56.8% (95% CI, 50.0%-63.4%) of patients in the camrelizumab-chemotherapy group vs 44.7% (95% CI, 38.0%-51.6%) in the placebo-chemotherapy group (rate difference, 12.2%; 95% CI, 3.3%-21.2%; P = .004).
• Grade 3 or higher adverse events occurred in 89.2% of camrelizumab-chemotherapy group vs 83.1% in placebo-chemotherapy group, with serious adverse events in 34.7% vs 22.8%, respectively.
• Event-free survival rate at 18 months was 86.6% (95% CI, 79.9%-91.1%) with camrelizumab-chemotherapy vs 83.6% (95% CI, 76.2%-88.9%) with placebo-chemotherapy (hazard ratio [HR], 0.80; 95% CI, 0.46-1.42).
• Disease-free survival rate at 12 months reached 91.9% (95% CI, 85.5%-95.5%) with camrelizumab-chemotherapy compared with 87.8% (95% CI, 80.3%-92.6%) with placebo-chemotherapy (HR, 0.58; 95% CI, 0.27-1.24).

IN PRACTICE:

“The addition of camrelizumab to neoadjuvant chemotherapy significantly improved pathological complete response... The benefits of camrelizumab-chemotherapy with respect to pCR were generally consistent across subgroups,” wrote the authors of the study.

SOURCE:

The study was led by Zhi-Ming Shao, MD, Fudan University Shanghai Cancer Center in Shanghai, China. It was published online on December 13 in JAMA.

LIMITATIONS:

According to the authors, the study’s limitations include short follow-up duration preventing assessment of mature survival data and long-term safety profile, uncertainty about optimal duration of adjuvant camrelizumab treatment, small sample sizes in some subgroups warranting cautious interpretation, and potential limited generalizability as the study was conducted only in Chinese patients with triple-negative breast cancer.

DISCLOSURES:

The study was supported by Jiangsu Hengrui Pharmaceuticals. The authors and funder were involved in data collection, analysis, and interpretation and guaranteed the accuracy, completeness of the data, writing of the report, and the decision to submit the manuscript for publication.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Adding camrelizumab to neoadjuvant chemotherapy increases pathological complete response rate to 56.8% vs 44.7% with placebo in early or locally advanced triple-negative breast cancer. The combination shows consistent benefits across patient subgroups with a manageable safety profile.

METHODOLOGY:

• A randomized, double-blind, phase 3 trial enrolled 441 females (median age, 48 years) with early or locally advanced triple-negative breast cancer from 40 hospitals in China between November 2020 and May 2023.
• Participants were randomized 1:1 to receive either camrelizumab 200 mg (n = 222) or placebo (n = 219) combined with chemotherapy every 2 weeks, with median follow-up period of 14.4 months.
• Treatment included nab-paclitaxel (100 mg/m²) plus carboplatin (area under curve, 1.5) on days 1, 8, and 15 in 28-day cycles for 16 weeks, followed by epirubicin (90 mg/m²) and cyclophosphamide (500 mg/m²) every 2 weeks for 8 weeks.
• The primary endpoint was pathological complete response, defined as no invasive tumor in breast and lymph nodes.

TAKEAWAY:

• Pathological complete response was achieved in 56.8% (95% CI, 50.0%-63.4%) of patients in the camrelizumab-chemotherapy group vs 44.7% (95% CI, 38.0%-51.6%) in the placebo-chemotherapy group (rate difference, 12.2%; 95% CI, 3.3%-21.2%; P = .004).
• Grade 3 or higher adverse events occurred in 89.2% of camrelizumab-chemotherapy group vs 83.1% in placebo-chemotherapy group, with serious adverse events in 34.7% vs 22.8%, respectively.
• Event-free survival rate at 18 months was 86.6% (95% CI, 79.9%-91.1%) with camrelizumab-chemotherapy vs 83.6% (95% CI, 76.2%-88.9%) with placebo-chemotherapy (hazard ratio [HR], 0.80; 95% CI, 0.46-1.42).
• Disease-free survival rate at 12 months reached 91.9% (95% CI, 85.5%-95.5%) with camrelizumab-chemotherapy compared with 87.8% (95% CI, 80.3%-92.6%) with placebo-chemotherapy (HR, 0.58; 95% CI, 0.27-1.24).

IN PRACTICE:

“The addition of camrelizumab to neoadjuvant chemotherapy significantly improved pathological complete response... The benefits of camrelizumab-chemotherapy with respect to pCR were generally consistent across subgroups,” wrote the authors of the study.

SOURCE:

The study was led by Zhi-Ming Shao, MD, Fudan University Shanghai Cancer Center in Shanghai, China. It was published online on December 13 in JAMA.

LIMITATIONS:

According to the authors, the study’s limitations include short follow-up duration preventing assessment of mature survival data and long-term safety profile, uncertainty about optimal duration of adjuvant camrelizumab treatment, small sample sizes in some subgroups warranting cautious interpretation, and potential limited generalizability as the study was conducted only in Chinese patients with triple-negative breast cancer.

DISCLOSURES:

The study was supported by Jiangsu Hengrui Pharmaceuticals. The authors and funder were involved in data collection, analysis, and interpretation and guaranteed the accuracy, completeness of the data, writing of the report, and the decision to submit the manuscript for publication.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Adding camrelizumab to neoadjuvant chemotherapy increases pathological complete response rate to 56.8% vs 44.7% with placebo in early or locally advanced triple-negative breast cancer. The combination shows consistent benefits across patient subgroups with a manageable safety profile.

METHODOLOGY:

• A randomized, double-blind, phase 3 trial enrolled 441 females (median age, 48 years) with early or locally advanced triple-negative breast cancer from 40 hospitals in China between November 2020 and May 2023.
• Participants were randomized 1:1 to receive either camrelizumab 200 mg (n = 222) or placebo (n = 219) combined with chemotherapy every 2 weeks, with median follow-up period of 14.4 months.
• Treatment included nab-paclitaxel (100 mg/m²) plus carboplatin (area under curve, 1.5) on days 1, 8, and 15 in 28-day cycles for 16 weeks, followed by epirubicin (90 mg/m²) and cyclophosphamide (500 mg/m²) every 2 weeks for 8 weeks.
• The primary endpoint was pathological complete response, defined as no invasive tumor in breast and lymph nodes.

TAKEAWAY:

• Pathological complete response was achieved in 56.8% (95% CI, 50.0%-63.4%) of patients in the camrelizumab-chemotherapy group vs 44.7% (95% CI, 38.0%-51.6%) in the placebo-chemotherapy group (rate difference, 12.2%; 95% CI, 3.3%-21.2%; P = .004).
• Grade 3 or higher adverse events occurred in 89.2% of camrelizumab-chemotherapy group vs 83.1% in placebo-chemotherapy group, with serious adverse events in 34.7% vs 22.8%, respectively.
• Event-free survival rate at 18 months was 86.6% (95% CI, 79.9%-91.1%) with camrelizumab-chemotherapy vs 83.6% (95% CI, 76.2%-88.9%) with placebo-chemotherapy (hazard ratio [HR], 0.80; 95% CI, 0.46-1.42).
• Disease-free survival rate at 12 months reached 91.9% (95% CI, 85.5%-95.5%) with camrelizumab-chemotherapy compared with 87.8% (95% CI, 80.3%-92.6%) with placebo-chemotherapy (HR, 0.58; 95% CI, 0.27-1.24).

IN PRACTICE:

“The addition of camrelizumab to neoadjuvant chemotherapy significantly improved pathological complete response... The benefits of camrelizumab-chemotherapy with respect to pCR were generally consistent across subgroups,” wrote the authors of the study.

SOURCE:

The study was led by Zhi-Ming Shao, MD, Fudan University Shanghai Cancer Center in Shanghai, China. It was published online on December 13 in JAMA.

LIMITATIONS:

According to the authors, the study’s limitations include short follow-up duration preventing assessment of mature survival data and long-term safety profile, uncertainty about optimal duration of adjuvant camrelizumab treatment, small sample sizes in some subgroups warranting cautious interpretation, and potential limited generalizability as the study was conducted only in Chinese patients with triple-negative breast cancer.

DISCLOSURES:

The study was supported by Jiangsu Hengrui Pharmaceuticals. The authors and funder were involved in data collection, analysis, and interpretation and guaranteed the accuracy, completeness of the data, writing of the report, and the decision to submit the manuscript for publication.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

SAN ANTONIO — A large trial has begun to make the case for active surveillance as an alternative to immediate surgery for low-risk ductal carcinoma in situ (DCIS).

At 2 years, investigators on the COMET trial found no clinically meaningful difference in the rates of ipsilateral invasive breast cancer among women randomized to active surveillance vs standard upfront surgery with or without radiation.

The 2-year findings suggest that surveillance is safe in the short term.

“While these results are provocative, I don’t think they’re quite practice-changing yet,” said lead investigator Shelley Hwang, MD, a surgical breast oncologist at Duke University in Durham, North Carolina, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024.

For one thing, it generally takes longer than 2 years for DCIS to convert to invasive cancer, so it will be important to wait for the planned analyses at 5, 7, and 10 years to make sure there isn’t an excess number of invasive breast cancers in the surveillance arm, Hwang said.

If the results prove durable, however, the findings will likely be “practice-changing” for women who were at least 40 years old and had grade 1 or 2 hormone receptor–positive DCIS at low risk for conversion, Hwang said.

The goal of active surveillance is to prevent unnecessary treatment. During surveillance, lesions are monitored for changes that indicate conversion to more advanced disease, at which point guideline-concordant care begins.

Although DCIS can convert to invasive breast cancer, this doesn’t always happen. As a result, upfront surgery and radiation aren’t necessary for some women.

The COMET trial aimed to determine the short-term safety of an active monitoring approach compared with guideline-concordant care in patients with low-risk DCIS.

The prospective, randomized noninferiority trial included women aged 40 years or older with a new diagnosis of HR–positive grade 1 or grade 2 DCIS without invasive cancer from 100 US Alliance Cancer Cooperative Group clinical trial sites.

In the trial, 484 women with DCIS were randomized to active surveillance — breast mammography and physical exam every 6 months — and 473 were randomized to standard upfront surgery with or without radiation. Overall, 15.7% of participants were Black and 75.0% were White.

Patients in either group could elect to have endocrine therapy, typically over a 5-year period (71% of women in the active monitoring group and 65.5% in the surgery group opted for endocrine therapy).

At 2 years, the cumulative rate of ipsilateral invasive breast cancer was 4.2% in the surveillance group vs 5.9% in the upfront surgery arm.

The study also included a planned per-protocol analysis among 673 patients who strictly followed the study protocol — 246 in the guideline-concordant care group who had received surgery by 6 months and 427 in the surveillance group who initiated the active monitoring protocol at 6 months.

With almost half of patients randomized to surgery declined to have it, which indicates that patients are interested in active monitoring, Hwang said.

At 2 years, the cumulative rate of invasive breast cancer was 3.1% in the active surveillance group vs 8.7% in the upfront surgery arm.

Among patients receiving endocrine therapy, the rate of invasive cancer was 7.15% in the surgery group and 3.21% in the surveillance arm.

Endocrine therapy “may have resulted in a reduced rate of invasive cancer in the active monitoring group,” the study authors noted.

These findings bring up the question of whether endocrine therapy might be just as good as surgery for low-risk DCIS, Hwang added. Given that one third of women undergo mastectomy for DCIS, “I think it’s not an inconsequential question,” Hwang said.

The findings, however, also suggest that surveillance sometimes leaves invasive cancer behind, Hwang explained. Nearly all invasive cancers in the surgery group were found during the initial operation , which may explain the slightly higher rates of invasive cancers in this group. Had the active monitoring group undergone surgery as well, the incidence of invasive cancer may have been the same in both arms, Hwang said.

However, when invasive cancers were removed, there were no significant differences in tumor size, node status, or tumor grade between the two groups, suggesting that there might not be a clinical penalty for delayed intervention with active monitoring, Hwang said.

With more than 10% of patients in the surgery group opting for mastectomy, compared with 1.8% in the active monitoring group, the active monitoring approach may not increase the likelihood of an eventual need for more extensive surgery, the COMET authors explained.

 

What Strategy Do Patients Prefer?

A companion analysis of patient-reported outcomes in COMET found no meaningful differences in quality of life, symptoms, or anxiety among patients who opted for surveillance over surgery. Results from questionnaires on quality of life, anxiety, depression, and breast cancer concerns were comparable between the two groups, with no evidence of a substantial impact of one approach over the other at 2 years.

“The results of this secondary analysis suggest that the lived experiences of individuals with low-risk DCIS are similar during early follow-up regardless of treatment allocation,” the COMET investigators concluded.

Overall, the findings from COMET provide reassuring short-term data, said Neil Iyengar, MD, a medical breast oncologist at Memorial Sloan Kettering Cancer Center in New York City.

DCIS is not an aggressive cancer, and it’s not going to invade any time soon, so patients have time to consider their options, Iyengar told Medscape Medical News.

The 2-year findings from COMET also help inform patient discussions. “I can tell patients if they decide not to have surgery what the likelihood is that they are going to convert into invasive cancer” after 2 years, he said.

COMET was published in JAMA, and the PRO analysis was published in JAMA Oncology to coincide with the study presentations.

COMET is funded by the Patient-Centered Outcomes Research Institute and others. Hwang is a consultant for Merck and on the advisory board of Clinetic, Exai Bio, and Havah Therapeutics. Iyengar is an advisor and/or researcher for AstraZeneca, Novartis, Pfizer, and other companies.

A version of this article first appeared on Medscape.com.

SAN ANTONIO — A large trial has begun to make the case for active surveillance as an alternative to immediate surgery for low-risk ductal carcinoma in situ (DCIS).

At 2 years, investigators on the COMET trial found no clinically meaningful difference in the rates of ipsilateral invasive breast cancer among women randomized to active surveillance vs standard upfront surgery with or without radiation.

The 2-year findings suggest that surveillance is safe in the short term.

“While these results are provocative, I don’t think they’re quite practice-changing yet,” said lead investigator Shelley Hwang, MD, a surgical breast oncologist at Duke University in Durham, North Carolina, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024.

For one thing, it generally takes longer than 2 years for DCIS to convert to invasive cancer, so it will be important to wait for the planned analyses at 5, 7, and 10 years to make sure there isn’t an excess number of invasive breast cancers in the surveillance arm, Hwang said.

If the results prove durable, however, the findings will likely be “practice-changing” for women who were at least 40 years old and had grade 1 or 2 hormone receptor–positive DCIS at low risk for conversion, Hwang said.

The goal of active surveillance is to prevent unnecessary treatment. During surveillance, lesions are monitored for changes that indicate conversion to more advanced disease, at which point guideline-concordant care begins.

Although DCIS can convert to invasive breast cancer, this doesn’t always happen. As a result, upfront surgery and radiation aren’t necessary for some women.

The COMET trial aimed to determine the short-term safety of an active monitoring approach compared with guideline-concordant care in patients with low-risk DCIS.

The prospective, randomized noninferiority trial included women aged 40 years or older with a new diagnosis of HR–positive grade 1 or grade 2 DCIS without invasive cancer from 100 US Alliance Cancer Cooperative Group clinical trial sites.

In the trial, 484 women with DCIS were randomized to active surveillance — breast mammography and physical exam every 6 months — and 473 were randomized to standard upfront surgery with or without radiation. Overall, 15.7% of participants were Black and 75.0% were White.

Patients in either group could elect to have endocrine therapy, typically over a 5-year period (71% of women in the active monitoring group and 65.5% in the surgery group opted for endocrine therapy).

At 2 years, the cumulative rate of ipsilateral invasive breast cancer was 4.2% in the surveillance group vs 5.9% in the upfront surgery arm.

The study also included a planned per-protocol analysis among 673 patients who strictly followed the study protocol — 246 in the guideline-concordant care group who had received surgery by 6 months and 427 in the surveillance group who initiated the active monitoring protocol at 6 months.

With almost half of patients randomized to surgery declined to have it, which indicates that patients are interested in active monitoring, Hwang said.

At 2 years, the cumulative rate of invasive breast cancer was 3.1% in the active surveillance group vs 8.7% in the upfront surgery arm.

Among patients receiving endocrine therapy, the rate of invasive cancer was 7.15% in the surgery group and 3.21% in the surveillance arm.

Endocrine therapy “may have resulted in a reduced rate of invasive cancer in the active monitoring group,” the study authors noted.

These findings bring up the question of whether endocrine therapy might be just as good as surgery for low-risk DCIS, Hwang added. Given that one third of women undergo mastectomy for DCIS, “I think it’s not an inconsequential question,” Hwang said.

The findings, however, also suggest that surveillance sometimes leaves invasive cancer behind, Hwang explained. Nearly all invasive cancers in the surgery group were found during the initial operation , which may explain the slightly higher rates of invasive cancers in this group. Had the active monitoring group undergone surgery as well, the incidence of invasive cancer may have been the same in both arms, Hwang said.

However, when invasive cancers were removed, there were no significant differences in tumor size, node status, or tumor grade between the two groups, suggesting that there might not be a clinical penalty for delayed intervention with active monitoring, Hwang said.

With more than 10% of patients in the surgery group opting for mastectomy, compared with 1.8% in the active monitoring group, the active monitoring approach may not increase the likelihood of an eventual need for more extensive surgery, the COMET authors explained.

 

What Strategy Do Patients Prefer?

A companion analysis of patient-reported outcomes in COMET found no meaningful differences in quality of life, symptoms, or anxiety among patients who opted for surveillance over surgery. Results from questionnaires on quality of life, anxiety, depression, and breast cancer concerns were comparable between the two groups, with no evidence of a substantial impact of one approach over the other at 2 years.

“The results of this secondary analysis suggest that the lived experiences of individuals with low-risk DCIS are similar during early follow-up regardless of treatment allocation,” the COMET investigators concluded.

Overall, the findings from COMET provide reassuring short-term data, said Neil Iyengar, MD, a medical breast oncologist at Memorial Sloan Kettering Cancer Center in New York City.

DCIS is not an aggressive cancer, and it’s not going to invade any time soon, so patients have time to consider their options, Iyengar told Medscape Medical News.

The 2-year findings from COMET also help inform patient discussions. “I can tell patients if they decide not to have surgery what the likelihood is that they are going to convert into invasive cancer” after 2 years, he said.

COMET was published in JAMA, and the PRO analysis was published in JAMA Oncology to coincide with the study presentations.

COMET is funded by the Patient-Centered Outcomes Research Institute and others. Hwang is a consultant for Merck and on the advisory board of Clinetic, Exai Bio, and Havah Therapeutics. Iyengar is an advisor and/or researcher for AstraZeneca, Novartis, Pfizer, and other companies.

A version of this article first appeared on Medscape.com.

SAN ANTONIO — A large trial has begun to make the case for active surveillance as an alternative to immediate surgery for low-risk ductal carcinoma in situ (DCIS).

At 2 years, investigators on the COMET trial found no clinically meaningful difference in the rates of ipsilateral invasive breast cancer among women randomized to active surveillance vs standard upfront surgery with or without radiation.

The 2-year findings suggest that surveillance is safe in the short term.

“While these results are provocative, I don’t think they’re quite practice-changing yet,” said lead investigator Shelley Hwang, MD, a surgical breast oncologist at Duke University in Durham, North Carolina, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024.

For one thing, it generally takes longer than 2 years for DCIS to convert to invasive cancer, so it will be important to wait for the planned analyses at 5, 7, and 10 years to make sure there isn’t an excess number of invasive breast cancers in the surveillance arm, Hwang said.

If the results prove durable, however, the findings will likely be “practice-changing” for women who were at least 40 years old and had grade 1 or 2 hormone receptor–positive DCIS at low risk for conversion, Hwang said.

The goal of active surveillance is to prevent unnecessary treatment. During surveillance, lesions are monitored for changes that indicate conversion to more advanced disease, at which point guideline-concordant care begins.

Although DCIS can convert to invasive breast cancer, this doesn’t always happen. As a result, upfront surgery and radiation aren’t necessary for some women.

The COMET trial aimed to determine the short-term safety of an active monitoring approach compared with guideline-concordant care in patients with low-risk DCIS.

The prospective, randomized noninferiority trial included women aged 40 years or older with a new diagnosis of HR–positive grade 1 or grade 2 DCIS without invasive cancer from 100 US Alliance Cancer Cooperative Group clinical trial sites.

In the trial, 484 women with DCIS were randomized to active surveillance — breast mammography and physical exam every 6 months — and 473 were randomized to standard upfront surgery with or without radiation. Overall, 15.7% of participants were Black and 75.0% were White.

Patients in either group could elect to have endocrine therapy, typically over a 5-year period (71% of women in the active monitoring group and 65.5% in the surgery group opted for endocrine therapy).

At 2 years, the cumulative rate of ipsilateral invasive breast cancer was 4.2% in the surveillance group vs 5.9% in the upfront surgery arm.

The study also included a planned per-protocol analysis among 673 patients who strictly followed the study protocol — 246 in the guideline-concordant care group who had received surgery by 6 months and 427 in the surveillance group who initiated the active monitoring protocol at 6 months.

With almost half of patients randomized to surgery declined to have it, which indicates that patients are interested in active monitoring, Hwang said.

At 2 years, the cumulative rate of invasive breast cancer was 3.1% in the active surveillance group vs 8.7% in the upfront surgery arm.

Among patients receiving endocrine therapy, the rate of invasive cancer was 7.15% in the surgery group and 3.21% in the surveillance arm.

Endocrine therapy “may have resulted in a reduced rate of invasive cancer in the active monitoring group,” the study authors noted.

These findings bring up the question of whether endocrine therapy might be just as good as surgery for low-risk DCIS, Hwang added. Given that one third of women undergo mastectomy for DCIS, “I think it’s not an inconsequential question,” Hwang said.

The findings, however, also suggest that surveillance sometimes leaves invasive cancer behind, Hwang explained. Nearly all invasive cancers in the surgery group were found during the initial operation , which may explain the slightly higher rates of invasive cancers in this group. Had the active monitoring group undergone surgery as well, the incidence of invasive cancer may have been the same in both arms, Hwang said.

However, when invasive cancers were removed, there were no significant differences in tumor size, node status, or tumor grade between the two groups, suggesting that there might not be a clinical penalty for delayed intervention with active monitoring, Hwang said.

With more than 10% of patients in the surgery group opting for mastectomy, compared with 1.8% in the active monitoring group, the active monitoring approach may not increase the likelihood of an eventual need for more extensive surgery, the COMET authors explained.

 

What Strategy Do Patients Prefer?

A companion analysis of patient-reported outcomes in COMET found no meaningful differences in quality of life, symptoms, or anxiety among patients who opted for surveillance over surgery. Results from questionnaires on quality of life, anxiety, depression, and breast cancer concerns were comparable between the two groups, with no evidence of a substantial impact of one approach over the other at 2 years.

“The results of this secondary analysis suggest that the lived experiences of individuals with low-risk DCIS are similar during early follow-up regardless of treatment allocation,” the COMET investigators concluded.

Overall, the findings from COMET provide reassuring short-term data, said Neil Iyengar, MD, a medical breast oncologist at Memorial Sloan Kettering Cancer Center in New York City.

DCIS is not an aggressive cancer, and it’s not going to invade any time soon, so patients have time to consider their options, Iyengar told Medscape Medical News.

The 2-year findings from COMET also help inform patient discussions. “I can tell patients if they decide not to have surgery what the likelihood is that they are going to convert into invasive cancer” after 2 years, he said.

COMET was published in JAMA, and the PRO analysis was published in JAMA Oncology to coincide with the study presentations.

COMET is funded by the Patient-Centered Outcomes Research Institute and others. Hwang is a consultant for Merck and on the advisory board of Clinetic, Exai Bio, and Havah Therapeutics. Iyengar is an advisor and/or researcher for AstraZeneca, Novartis, Pfizer, and other companies.

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the immune checkpoint inhibitor cosibelimab (Unloxcyt; Checkpoint Therapeutics) for the treatment of adults with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation. 

The programmed death ligand-1 (PD-L1)–blocking antibody is the first and only treatment of its kind approved for advanced CSCC, according to a Checkpoint Therapeutics press release. The FDA approval was based on findings from the multicenter, open-label Study CK-301-101 trial of 109 patients. 

In that trial, the objective response rate (ORR) was 47% in 78 patients with metastatic CSCC and 48% in 31 patients with locally advanced CSCC. Median duration of response (DOR) in treated patients was not reached in those with metastatic disease and was 17.7 months in those with locally advanced disease, according to the FDA approval notice.

Adverse reactions occurring in at least 10% of patients included fatigue, musculoskeletal pain, rash, diarrhea, hypothyroidism, constipation, nausea, headache, pruritus, edema, localized infection, and urinary tract infection.

The recommended treatment dose, according to the prescribing information, is 1200 mg given as an intravenous infusion over 60 minutes every 3 weeks until disease progression or unacceptable toxicity.

The agent offers “a differentiated treatment option versus available therapies by binding to PD-L1, rather than programmed death receptor-1 (PD-1), to release the inhibitory effects of PD-L1 on the anti-tumor immune response,” Checkpoint Therapeutics president and chief executive officer James Oliviero stated in the company press release. 

The agent has also “demonstrated the ability to induce antibody-dependent cell-mediated cytotoxicity, another potential differentiating feature of the drug compared to existing marketing therapies for CSCC,” Oliviero noted.

“CSCC is the second most common form of skin cancer, and those diagnosed with advanced disease that has recurred or metastasized face a poor prognosis,” stated Emily Ruiz, MD, academic director of the Mohs and Dermatologic Surgery Center at Brigham and Women’s Hospital and director of the High-Risk Skin Cancer Clinic at Dana-Farber Brigham Cancer Center. 

“With its dual mechanisms of action and compelling safety profile, this promising drug will provide US oncologists with an important new immunotherapy option for the treatment of CSCC,” she added. 

 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the immune checkpoint inhibitor cosibelimab (Unloxcyt; Checkpoint Therapeutics) for the treatment of adults with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation. 

The programmed death ligand-1 (PD-L1)–blocking antibody is the first and only treatment of its kind approved for advanced CSCC, according to a Checkpoint Therapeutics press release. The FDA approval was based on findings from the multicenter, open-label Study CK-301-101 trial of 109 patients. 

In that trial, the objective response rate (ORR) was 47% in 78 patients with metastatic CSCC and 48% in 31 patients with locally advanced CSCC. Median duration of response (DOR) in treated patients was not reached in those with metastatic disease and was 17.7 months in those with locally advanced disease, according to the FDA approval notice.

Adverse reactions occurring in at least 10% of patients included fatigue, musculoskeletal pain, rash, diarrhea, hypothyroidism, constipation, nausea, headache, pruritus, edema, localized infection, and urinary tract infection.

The recommended treatment dose, according to the prescribing information, is 1200 mg given as an intravenous infusion over 60 minutes every 3 weeks until disease progression or unacceptable toxicity.

The agent offers “a differentiated treatment option versus available therapies by binding to PD-L1, rather than programmed death receptor-1 (PD-1), to release the inhibitory effects of PD-L1 on the anti-tumor immune response,” Checkpoint Therapeutics president and chief executive officer James Oliviero stated in the company press release. 

The agent has also “demonstrated the ability to induce antibody-dependent cell-mediated cytotoxicity, another potential differentiating feature of the drug compared to existing marketing therapies for CSCC,” Oliviero noted.

“CSCC is the second most common form of skin cancer, and those diagnosed with advanced disease that has recurred or metastasized face a poor prognosis,” stated Emily Ruiz, MD, academic director of the Mohs and Dermatologic Surgery Center at Brigham and Women’s Hospital and director of the High-Risk Skin Cancer Clinic at Dana-Farber Brigham Cancer Center. 

“With its dual mechanisms of action and compelling safety profile, this promising drug will provide US oncologists with an important new immunotherapy option for the treatment of CSCC,” she added. 

 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved the immune checkpoint inhibitor cosibelimab (Unloxcyt; Checkpoint Therapeutics) for the treatment of adults with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation. 

The programmed death ligand-1 (PD-L1)–blocking antibody is the first and only treatment of its kind approved for advanced CSCC, according to a Checkpoint Therapeutics press release. The FDA approval was based on findings from the multicenter, open-label Study CK-301-101 trial of 109 patients. 

In that trial, the objective response rate (ORR) was 47% in 78 patients with metastatic CSCC and 48% in 31 patients with locally advanced CSCC. Median duration of response (DOR) in treated patients was not reached in those with metastatic disease and was 17.7 months in those with locally advanced disease, according to the FDA approval notice.

Adverse reactions occurring in at least 10% of patients included fatigue, musculoskeletal pain, rash, diarrhea, hypothyroidism, constipation, nausea, headache, pruritus, edema, localized infection, and urinary tract infection.

The recommended treatment dose, according to the prescribing information, is 1200 mg given as an intravenous infusion over 60 minutes every 3 weeks until disease progression or unacceptable toxicity.

The agent offers “a differentiated treatment option versus available therapies by binding to PD-L1, rather than programmed death receptor-1 (PD-1), to release the inhibitory effects of PD-L1 on the anti-tumor immune response,” Checkpoint Therapeutics president and chief executive officer James Oliviero stated in the company press release. 

The agent has also “demonstrated the ability to induce antibody-dependent cell-mediated cytotoxicity, another potential differentiating feature of the drug compared to existing marketing therapies for CSCC,” Oliviero noted.

“CSCC is the second most common form of skin cancer, and those diagnosed with advanced disease that has recurred or metastasized face a poor prognosis,” stated Emily Ruiz, MD, academic director of the Mohs and Dermatologic Surgery Center at Brigham and Women’s Hospital and director of the High-Risk Skin Cancer Clinic at Dana-Farber Brigham Cancer Center. 

“With its dual mechanisms of action and compelling safety profile, this promising drug will provide US oncologists with an important new immunotherapy option for the treatment of CSCC,” she added. 

 

A version of this article appeared on Medscape.com.

Long COVID can have an enormous impact on people’s ability to work, particularly if they do not have workplace accommodations and support. Although some patients experience symptoms so severe that they cannot work under any conditions, medical providers and employers can help ensure many patients with long COVID can stay in the workforce.

Long COVID is an infection-associated chronic condition that occurs after SARS-CoV-2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems. By the end of 2023, at least 400 million people worldwide were estimated to have long COVID.

As members of the Patient-Led Research Collaborative, an international group of more than 60 researchers and health advocates living with long COVID and other infection-associated chronic conditions, we have published one of the first research studies of people with long COVID and their desire to work, the specific needs they have, and what doctors and employers can do to create a path for returning to the workforce. 

In our recent paper, we document the barriers and facilitators that individuals living with long COVID experience when attempting to return to work. Our recommendations are based on these findings and include recommendations for both medical providers and employers. 

If you are a medical provider:

• Ensure you adequately document your patients’ COVID cases, any long COVID diagnoses, and the functional impairment that long COVID causes. Remember that you can diagnose a patient with long COVID on the basis of their symptoms, and clinical guidelines do not require a record of a positive COVID-19 test, which many patients lack owing to testing barriers.
• Keep up to date on research on long COVID and related infection-associated chronic conditions — for example, through the Project ECHO Long COVID and Fatiguing Illness Recovery Program — and learn about pacing and other treatment options.

If you are an employer: 

• Utilize a return-to-work model in which any worker with suspected or confirmed COVID discusses support they may need with their employer when they return to work, with additional check-in dates scheduled to reevaluate supports as needed. Planning for this collaborative and iterative evaluation of return-to-work supports for all workers with COVID-19 is important because it may not be immediately clear to a worker whether they have developed long COVID or are generally recuperating from the illness.
• Do not require medical documentation of a SARS-CoV-2 infection or a Long COVID diagnosis to access accommodations — this is owing to disparities in accessing documentation.
• Tailor job responsibilities, provide remote options, allow flexible hours, and provide longer-range deadlines to account for symptoms for people with long COVID and other infection-associated chronic conditions.
• Provide accommodations to any caregivers of people with long COVID in your workplace.
• If requiring in-person work, make the workplace as safe as possible through ventilation and masking requirements, which will help ensure fewer of your workers develop long COVID, and those already with infection-associated chronic conditions will not get worse.

Our findings and recommendations are specific to long COVID, but they can and should apply to other disabilities. Given that our study’s sample was predominately White and working in jobs that did not require substantial physical labor, additional recommendations may be needed for other populations and workers who have labor-intensive jobs.

 

510 Study Participants

Long COVID is characterized as a relapsing-remitting illness, often described as episodic, in which an individual’s symptoms may fluctuate. Symptoms can become more or less severe depending on tasks, exertion, and social support in addition to physiologic processes and medical intervention. In our paper, we illustrate how the long COVID return-to-work experience and individuals’ symptoms can be shaped by workplace, home, and medical environments. 

We randomly selected 510 participants from a global survey of people living with long COVID and systematically analyzed their open-ended responses using established qualitative analysis methods. In this study, we specifically analyzed what patients wrote about their return-to-work experiences, considering how work experiences and relapsing and remitting long COVID symptoms intersected with personal lives and medical care. 

Most of the study participants identified as White, were 30-60 years old (ie, in their key earning years), and had at least a baccalaureate degree. Participants lived in the United States (38%), United Kingdom (25%), continental Europe (8%), Canada (4%), or other countries (25%). Most participants worked in professions that did not require substantial physical labor, and individuals in those fields may experience even greater return-to-work barriers than are reported in this study.

 

Key Findings

Through our qualitative analysis, we identified four primary return-to-work themes: 

1. People living with long COVID have a strong desire and financial need to return to work. 

The participants in our study described how they had experienced financial hardship because they could not successfully return to work and may have incurred new expenses with long COVID. They also often wrote how they wanted to return to work because their jobs provided meaning and structure for their lives. Some people in this study shared how they had tried to return to their jobs but relapsed. As a result, they considered leaving the workforce.

2. Workers’ long COVID symptoms intersect with organization of work and home life.

Most of the people in our study were employed in positions that did not require substantial physical labor. Even so, workers described how their long COVID symptoms were exacerbated by some job tasks. Computer screen time; reading dense material or writing (including emails); and conversations and meetings, regardless of whether they were in-person or via phone or video conferencing, could trigger or make symptoms worse. Workers who needed to stand for long periods of time, such as teachers and healthcare workers, and workers who needed to do lifting as part of their jobs described how these requirements were too taxing and could lead to relapses.

Because of the relapsing and remitting nature of many long COVID symptoms, people reported how it could be difficult to predict how job tasks, long hours, or pressing deadlines may exacerbate symptoms, which would require them to take time off work. For these participants, “pushing through” symptoms only made the symptoms worse. However, people in the study who were allowed to work from home reported how pacing, elevating their legs, and conserving energy (especially by not commuting) was key to doing their jobs well.

Some people in the study described how they were only able to return to work because they had substantial support from family or partners at home. These individuals shared how the people they lived with did most of the cooking, cleaning, and other household tasks so that the person living with long COVID could conserve their energy for work. This reorganization of home life notably shifted household tasks and caregiving to other people in the household, but without this shift, the individual’s long COVID symptoms may be too severe to work.

3. People with long COVID experience disbelief and stigma at work and healthcare settings.

Some people in our study described how their colleagues, supervisors, and human resource managers insinuated that they were fabricating or exaggerating their symptoms. This made it hard for workers to communicate what support they needed and could limit access to necessary work accommodations.

Many people in our study also described how medical providers did not believe that they had long COVID despite experiencing debilitating symptoms, often because they did not have a positive COVID-19 test to prove they had had an acute infection. Many people with long COVID may not have a positive COVID-19 test because:

• They could not access a test because testing access was limited at the start of the COVID-19 pandemic, there are transportation and cost barriers to tests, many health insurance providers no longer cover tests; and there are fewer public testing sites since the World Health Organization declared an end to the public health emergency;
• There is a high probability of false-negative results for viral and antibody tests (especially during the first wave of the pandemic and for individuals with limited immune response); and
• People can develop long COVID after asymptomatic acute infection.

Although healthcare providers can provide a long COVID diagnosis without a positive COVID-19 test on the basis of a patient’s presentation of symptoms and clinical history, many people in our study said that their providers would not provide this diagnosis, which restricted access to worker’s compensation, paid time off, and job accommodations.

Many people in the study also reported that their medical providers misdiagnosed them with a mental health disorder, such as anxiety, instead of long COVID. Although some people with long COVID may experience poor mental health as a natural consequence of dealing with a debilitating medical condition or may have neuropsychiatric symptoms as part of their long COVID, long COVID is not caused by an underlying psychiatric illness.

4. Support of medical providers is key to successful return to work for people living with long COVID.

Some people in our study described how they were able to get workplace accommodations or access workers’ compensation or sick leave because their medical providers recognized they had long COVID and provided them with this documentation. Some of these participants did not have a positive COVID-19 test, but their medical providers were able to diagnose them with long COVID on the basis of symptom presentation and clinical history. This documentation was critical for helping workers remain financially stable and able to return to work.

 

Conclusion

While we continue to search for treatment and cures for long COVID and work to provide a robust social safety net, it is crucial to address the stigma, inaccessibility, and lack of support often experienced by patients in their workplaces. Disabled people have long faced these issues; long COVID may be an opportunity to revolutionize the workplace to ensure an inclusive and accessible environment that can improve the lives of all workers.

For more on how to best be inclusive of employees with long COVID, read Harvard Business Review’s “Long Covid at Work: A Manager’s Guide” and visit the Job Accommodation Network webpage dedicated to long COVID.

Additional discussion about our study and applying the findings to improve work and medical care can be found by listening to the Healthy Work podcast episode titled “Supporting Long COVID at Work.” 

 

Elisabeth Stelson, Gina Assaf, and Lisa McCorkell are members of the Patient-Led Research Collaborative, an international group of more than 60 researchers. Dr Stelson, Postdoctoral Research Fellow, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, has disclosed no relevant financial relationships. Gina Assaf is Research Lead, Patient-Led Research Collaborative, Washington, DC. Lisa McCorkell is a long COVID patient; Cofounder, Team Lead, Researcher, Patient-Led Research Collaborative, Washington, DC.

A version of this article appeared on Medscape.com.

Long COVID can have an enormous impact on people’s ability to work, particularly if they do not have workplace accommodations and support. Although some patients experience symptoms so severe that they cannot work under any conditions, medical providers and employers can help ensure many patients with long COVID can stay in the workforce.

Long COVID is an infection-associated chronic condition that occurs after SARS-CoV-2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems. By the end of 2023, at least 400 million people worldwide were estimated to have long COVID.

As members of the Patient-Led Research Collaborative, an international group of more than 60 researchers and health advocates living with long COVID and other infection-associated chronic conditions, we have published one of the first research studies of people with long COVID and their desire to work, the specific needs they have, and what doctors and employers can do to create a path for returning to the workforce. 

In our recent paper, we document the barriers and facilitators that individuals living with long COVID experience when attempting to return to work. Our recommendations are based on these findings and include recommendations for both medical providers and employers. 

If you are a medical provider:

• Ensure you adequately document your patients’ COVID cases, any long COVID diagnoses, and the functional impairment that long COVID causes. Remember that you can diagnose a patient with long COVID on the basis of their symptoms, and clinical guidelines do not require a record of a positive COVID-19 test, which many patients lack owing to testing barriers.
• Keep up to date on research on long COVID and related infection-associated chronic conditions — for example, through the Project ECHO Long COVID and Fatiguing Illness Recovery Program — and learn about pacing and other treatment options.

If you are an employer: 

• Utilize a return-to-work model in which any worker with suspected or confirmed COVID discusses support they may need with their employer when they return to work, with additional check-in dates scheduled to reevaluate supports as needed. Planning for this collaborative and iterative evaluation of return-to-work supports for all workers with COVID-19 is important because it may not be immediately clear to a worker whether they have developed long COVID or are generally recuperating from the illness.
• Do not require medical documentation of a SARS-CoV-2 infection or a Long COVID diagnosis to access accommodations — this is owing to disparities in accessing documentation.
• Tailor job responsibilities, provide remote options, allow flexible hours, and provide longer-range deadlines to account for symptoms for people with long COVID and other infection-associated chronic conditions.
• Provide accommodations to any caregivers of people with long COVID in your workplace.
• If requiring in-person work, make the workplace as safe as possible through ventilation and masking requirements, which will help ensure fewer of your workers develop long COVID, and those already with infection-associated chronic conditions will not get worse.

Our findings and recommendations are specific to long COVID, but they can and should apply to other disabilities. Given that our study’s sample was predominately White and working in jobs that did not require substantial physical labor, additional recommendations may be needed for other populations and workers who have labor-intensive jobs.

 

510 Study Participants

Long COVID is characterized as a relapsing-remitting illness, often described as episodic, in which an individual’s symptoms may fluctuate. Symptoms can become more or less severe depending on tasks, exertion, and social support in addition to physiologic processes and medical intervention. In our paper, we illustrate how the long COVID return-to-work experience and individuals’ symptoms can be shaped by workplace, home, and medical environments. 

We randomly selected 510 participants from a global survey of people living with long COVID and systematically analyzed their open-ended responses using established qualitative analysis methods. In this study, we specifically analyzed what patients wrote about their return-to-work experiences, considering how work experiences and relapsing and remitting long COVID symptoms intersected with personal lives and medical care. 

Most of the study participants identified as White, were 30-60 years old (ie, in their key earning years), and had at least a baccalaureate degree. Participants lived in the United States (38%), United Kingdom (25%), continental Europe (8%), Canada (4%), or other countries (25%). Most participants worked in professions that did not require substantial physical labor, and individuals in those fields may experience even greater return-to-work barriers than are reported in this study.

 

Key Findings

Through our qualitative analysis, we identified four primary return-to-work themes: 

1. People living with long COVID have a strong desire and financial need to return to work. 

The participants in our study described how they had experienced financial hardship because they could not successfully return to work and may have incurred new expenses with long COVID. They also often wrote how they wanted to return to work because their jobs provided meaning and structure for their lives. Some people in this study shared how they had tried to return to their jobs but relapsed. As a result, they considered leaving the workforce.

2. Workers’ long COVID symptoms intersect with organization of work and home life.

Most of the people in our study were employed in positions that did not require substantial physical labor. Even so, workers described how their long COVID symptoms were exacerbated by some job tasks. Computer screen time; reading dense material or writing (including emails); and conversations and meetings, regardless of whether they were in-person or via phone or video conferencing, could trigger or make symptoms worse. Workers who needed to stand for long periods of time, such as teachers and healthcare workers, and workers who needed to do lifting as part of their jobs described how these requirements were too taxing and could lead to relapses.

Because of the relapsing and remitting nature of many long COVID symptoms, people reported how it could be difficult to predict how job tasks, long hours, or pressing deadlines may exacerbate symptoms, which would require them to take time off work. For these participants, “pushing through” symptoms only made the symptoms worse. However, people in the study who were allowed to work from home reported how pacing, elevating their legs, and conserving energy (especially by not commuting) was key to doing their jobs well.

Some people in the study described how they were only able to return to work because they had substantial support from family or partners at home. These individuals shared how the people they lived with did most of the cooking, cleaning, and other household tasks so that the person living with long COVID could conserve their energy for work. This reorganization of home life notably shifted household tasks and caregiving to other people in the household, but without this shift, the individual’s long COVID symptoms may be too severe to work.

3. People with long COVID experience disbelief and stigma at work and healthcare settings.

Some people in our study described how their colleagues, supervisors, and human resource managers insinuated that they were fabricating or exaggerating their symptoms. This made it hard for workers to communicate what support they needed and could limit access to necessary work accommodations.

Many people in our study also described how medical providers did not believe that they had long COVID despite experiencing debilitating symptoms, often because they did not have a positive COVID-19 test to prove they had had an acute infection. Many people with long COVID may not have a positive COVID-19 test because:

• They could not access a test because testing access was limited at the start of the COVID-19 pandemic, there are transportation and cost barriers to tests, many health insurance providers no longer cover tests; and there are fewer public testing sites since the World Health Organization declared an end to the public health emergency;
• There is a high probability of false-negative results for viral and antibody tests (especially during the first wave of the pandemic and for individuals with limited immune response); and
• People can develop long COVID after asymptomatic acute infection.

Although healthcare providers can provide a long COVID diagnosis without a positive COVID-19 test on the basis of a patient’s presentation of symptoms and clinical history, many people in our study said that their providers would not provide this diagnosis, which restricted access to worker’s compensation, paid time off, and job accommodations.

Many people in the study also reported that their medical providers misdiagnosed them with a mental health disorder, such as anxiety, instead of long COVID. Although some people with long COVID may experience poor mental health as a natural consequence of dealing with a debilitating medical condition or may have neuropsychiatric symptoms as part of their long COVID, long COVID is not caused by an underlying psychiatric illness.

4. Support of medical providers is key to successful return to work for people living with long COVID.

Some people in our study described how they were able to get workplace accommodations or access workers’ compensation or sick leave because their medical providers recognized they had long COVID and provided them with this documentation. Some of these participants did not have a positive COVID-19 test, but their medical providers were able to diagnose them with long COVID on the basis of symptom presentation and clinical history. This documentation was critical for helping workers remain financially stable and able to return to work.

 

Conclusion

While we continue to search for treatment and cures for long COVID and work to provide a robust social safety net, it is crucial to address the stigma, inaccessibility, and lack of support often experienced by patients in their workplaces. Disabled people have long faced these issues; long COVID may be an opportunity to revolutionize the workplace to ensure an inclusive and accessible environment that can improve the lives of all workers.

For more on how to best be inclusive of employees with long COVID, read Harvard Business Review’s “Long Covid at Work: A Manager’s Guide” and visit the Job Accommodation Network webpage dedicated to long COVID.

Additional discussion about our study and applying the findings to improve work and medical care can be found by listening to the Healthy Work podcast episode titled “Supporting Long COVID at Work.” 

 

Elisabeth Stelson, Gina Assaf, and Lisa McCorkell are members of the Patient-Led Research Collaborative, an international group of more than 60 researchers. Dr Stelson, Postdoctoral Research Fellow, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, has disclosed no relevant financial relationships. Gina Assaf is Research Lead, Patient-Led Research Collaborative, Washington, DC. Lisa McCorkell is a long COVID patient; Cofounder, Team Lead, Researcher, Patient-Led Research Collaborative, Washington, DC.

A version of this article appeared on Medscape.com.

Long COVID can have an enormous impact on people’s ability to work, particularly if they do not have workplace accommodations and support. Although some patients experience symptoms so severe that they cannot work under any conditions, medical providers and employers can help ensure many patients with long COVID can stay in the workforce.

Long COVID is an infection-associated chronic condition that occurs after SARS-CoV-2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems. By the end of 2023, at least 400 million people worldwide were estimated to have long COVID.

As members of the Patient-Led Research Collaborative, an international group of more than 60 researchers and health advocates living with long COVID and other infection-associated chronic conditions, we have published one of the first research studies of people with long COVID and their desire to work, the specific needs they have, and what doctors and employers can do to create a path for returning to the workforce. 

In our recent paper, we document the barriers and facilitators that individuals living with long COVID experience when attempting to return to work. Our recommendations are based on these findings and include recommendations for both medical providers and employers. 

If you are a medical provider:

• Ensure you adequately document your patients’ COVID cases, any long COVID diagnoses, and the functional impairment that long COVID causes. Remember that you can diagnose a patient with long COVID on the basis of their symptoms, and clinical guidelines do not require a record of a positive COVID-19 test, which many patients lack owing to testing barriers.
• Keep up to date on research on long COVID and related infection-associated chronic conditions — for example, through the Project ECHO Long COVID and Fatiguing Illness Recovery Program — and learn about pacing and other treatment options.

If you are an employer: 

• Utilize a return-to-work model in which any worker with suspected or confirmed COVID discusses support they may need with their employer when they return to work, with additional check-in dates scheduled to reevaluate supports as needed. Planning for this collaborative and iterative evaluation of return-to-work supports for all workers with COVID-19 is important because it may not be immediately clear to a worker whether they have developed long COVID or are generally recuperating from the illness.
• Do not require medical documentation of a SARS-CoV-2 infection or a Long COVID diagnosis to access accommodations — this is owing to disparities in accessing documentation.
• Tailor job responsibilities, provide remote options, allow flexible hours, and provide longer-range deadlines to account for symptoms for people with long COVID and other infection-associated chronic conditions.
• Provide accommodations to any caregivers of people with long COVID in your workplace.
• If requiring in-person work, make the workplace as safe as possible through ventilation and masking requirements, which will help ensure fewer of your workers develop long COVID, and those already with infection-associated chronic conditions will not get worse.

Our findings and recommendations are specific to long COVID, but they can and should apply to other disabilities. Given that our study’s sample was predominately White and working in jobs that did not require substantial physical labor, additional recommendations may be needed for other populations and workers who have labor-intensive jobs.

 

510 Study Participants

Long COVID is characterized as a relapsing-remitting illness, often described as episodic, in which an individual’s symptoms may fluctuate. Symptoms can become more or less severe depending on tasks, exertion, and social support in addition to physiologic processes and medical intervention. In our paper, we illustrate how the long COVID return-to-work experience and individuals’ symptoms can be shaped by workplace, home, and medical environments. 

We randomly selected 510 participants from a global survey of people living with long COVID and systematically analyzed their open-ended responses using established qualitative analysis methods. In this study, we specifically analyzed what patients wrote about their return-to-work experiences, considering how work experiences and relapsing and remitting long COVID symptoms intersected with personal lives and medical care. 

Most of the study participants identified as White, were 30-60 years old (ie, in their key earning years), and had at least a baccalaureate degree. Participants lived in the United States (38%), United Kingdom (25%), continental Europe (8%), Canada (4%), or other countries (25%). Most participants worked in professions that did not require substantial physical labor, and individuals in those fields may experience even greater return-to-work barriers than are reported in this study.

 

Key Findings

Through our qualitative analysis, we identified four primary return-to-work themes: 

1. People living with long COVID have a strong desire and financial need to return to work. 

The participants in our study described how they had experienced financial hardship because they could not successfully return to work and may have incurred new expenses with long COVID. They also often wrote how they wanted to return to work because their jobs provided meaning and structure for their lives. Some people in this study shared how they had tried to return to their jobs but relapsed. As a result, they considered leaving the workforce.

2. Workers’ long COVID symptoms intersect with organization of work and home life.

Most of the people in our study were employed in positions that did not require substantial physical labor. Even so, workers described how their long COVID symptoms were exacerbated by some job tasks. Computer screen time; reading dense material or writing (including emails); and conversations and meetings, regardless of whether they were in-person or via phone or video conferencing, could trigger or make symptoms worse. Workers who needed to stand for long periods of time, such as teachers and healthcare workers, and workers who needed to do lifting as part of their jobs described how these requirements were too taxing and could lead to relapses.

Because of the relapsing and remitting nature of many long COVID symptoms, people reported how it could be difficult to predict how job tasks, long hours, or pressing deadlines may exacerbate symptoms, which would require them to take time off work. For these participants, “pushing through” symptoms only made the symptoms worse. However, people in the study who were allowed to work from home reported how pacing, elevating their legs, and conserving energy (especially by not commuting) was key to doing their jobs well.

Some people in the study described how they were only able to return to work because they had substantial support from family or partners at home. These individuals shared how the people they lived with did most of the cooking, cleaning, and other household tasks so that the person living with long COVID could conserve their energy for work. This reorganization of home life notably shifted household tasks and caregiving to other people in the household, but without this shift, the individual’s long COVID symptoms may be too severe to work.

3. People with long COVID experience disbelief and stigma at work and healthcare settings.

Some people in our study described how their colleagues, supervisors, and human resource managers insinuated that they were fabricating or exaggerating their symptoms. This made it hard for workers to communicate what support they needed and could limit access to necessary work accommodations.

Many people in our study also described how medical providers did not believe that they had long COVID despite experiencing debilitating symptoms, often because they did not have a positive COVID-19 test to prove they had had an acute infection. Many people with long COVID may not have a positive COVID-19 test because:

• They could not access a test because testing access was limited at the start of the COVID-19 pandemic, there are transportation and cost barriers to tests, many health insurance providers no longer cover tests; and there are fewer public testing sites since the World Health Organization declared an end to the public health emergency;
• There is a high probability of false-negative results for viral and antibody tests (especially during the first wave of the pandemic and for individuals with limited immune response); and
• People can develop long COVID after asymptomatic acute infection.

Although healthcare providers can provide a long COVID diagnosis without a positive COVID-19 test on the basis of a patient’s presentation of symptoms and clinical history, many people in our study said that their providers would not provide this diagnosis, which restricted access to worker’s compensation, paid time off, and job accommodations.

Many people in the study also reported that their medical providers misdiagnosed them with a mental health disorder, such as anxiety, instead of long COVID. Although some people with long COVID may experience poor mental health as a natural consequence of dealing with a debilitating medical condition or may have neuropsychiatric symptoms as part of their long COVID, long COVID is not caused by an underlying psychiatric illness.

4. Support of medical providers is key to successful return to work for people living with long COVID.

Some people in our study described how they were able to get workplace accommodations or access workers’ compensation or sick leave because their medical providers recognized they had long COVID and provided them with this documentation. Some of these participants did not have a positive COVID-19 test, but their medical providers were able to diagnose them with long COVID on the basis of symptom presentation and clinical history. This documentation was critical for helping workers remain financially stable and able to return to work.

 

Conclusion

While we continue to search for treatment and cures for long COVID and work to provide a robust social safety net, it is crucial to address the stigma, inaccessibility, and lack of support often experienced by patients in their workplaces. Disabled people have long faced these issues; long COVID may be an opportunity to revolutionize the workplace to ensure an inclusive and accessible environment that can improve the lives of all workers.

For more on how to best be inclusive of employees with long COVID, read Harvard Business Review’s “Long Covid at Work: A Manager’s Guide” and visit the Job Accommodation Network webpage dedicated to long COVID.

Additional discussion about our study and applying the findings to improve work and medical care can be found by listening to the Healthy Work podcast episode titled “Supporting Long COVID at Work.” 

 

Elisabeth Stelson, Gina Assaf, and Lisa McCorkell are members of the Patient-Led Research Collaborative, an international group of more than 60 researchers. Dr Stelson, Postdoctoral Research Fellow, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, has disclosed no relevant financial relationships. Gina Assaf is Research Lead, Patient-Led Research Collaborative, Washington, DC. Lisa McCorkell is a long COVID patient; Cofounder, Team Lead, Researcher, Patient-Led Research Collaborative, Washington, DC.

A version of this article appeared on Medscape.com.

An electronic nudge explaining the cardiovascular benefits of the influenza vaccine increased vaccination rates, particularly among people who had previously had a heart attack, showed the NUDGE FLU series of clinical trials.

Influenza has the potential to be a dangerous infection on its own, but it increases the risk for cardiovascular events among people with a history of heart attack, said the study’s lead author, Ankeet Bhatt, MD, a cardiologist at Kaiser Permanente San Francisco Medical Center, San Francisco.

“Yearly influenza vaccines help prevent influenza infection and, in patients with a heart attack, are potentially cardioprotective,” he said during his presentation at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago. The NUDGE FLU results were simultaneously published online in JAMA Cardiology.

In Denmark, where the trials were conducted, about 80% of older adults get flu shots, but only about 40% of younger adults with chronic diseases do, Bhatt reported. In the United States, about 45% of adults and 55% of children received at least one dose of the flu vaccine in the 2023/24 flu season, according to the US Centers for Disease Control and Prevention (CDC).

 

The NUDGE FLU Trials

Bhatt and his colleagues conducted three related clinical trials during the 2022/23 and 2023/24 flu seasons: NUDGE-FLU and NUDGE-FLU-2 targeted older adults, whereas NUDGE-FLU-CHRONIC targeted younger adults with chronic diseases. Nearly 2 million people were involved in the three trials.

Participants were randomized to receive one of a series of different behavioral-science-informed letters, delivered through a government-run electronic communication system, or no reminder.

People who received any of the nudges had higher rates of vaccination; among heart attack survivors, there was a 1.8% improvement and among adults without a history of heart attack, there was a 1.3% improvement. But a nudge that explained the potential cardiovascular benefits of flu shots was even more effective, leading to a 3.9% increase among people with a history of heart attack and a 2% increase among those with no heart attack history.

“A simple sentence resulted in a durable improvement in the vaccination rate,” said Bhatt.

The effect was even greater among those who had not been vaccinated in the previous flu season. Among heart attack survivors, nearly 14% more people got the vaccine compared with just 1.5% more survivors who were previously vaccinated. And it was most effective among younger adults who had experienced a recent heart attack, resulting in a 26% increase.

“The impact was larger in patients with a history of acute myocardial infarction, in those who were vaccine-hesitant, and in younger people” — all groups with the most to gain from vaccination in terms of cardiovascular protection — Bhatt reported.

About 25% of people in the United States are unsure about whether to get a flu shot, said Orly Vardeny, PharmD, professor of medicine at the University of Minnesota Medical School in Minneapolis, who was not involved in the study. The fact that previously unvaccinated people were convinced by the nudges is reassuring. “That’s the group where this intervention is most likely to move the needle,” she said.

Around half of all people hospitalized for flu in the United States have cardiovascular disease, CDC data showed, so “even a small increase in the number of patients who get vaccinated has substantial public health benefits,” Vardeny said.

The NUDGE FLU series showed that nudges like this should be employed as a simple tool to improve vaccination rates, but the system would be much more difficult to implement in the United States, Bhatt said.

Denmark has a national health service and a preexisting government electronic communication system, whereas the US system is privately run and more fractured. It would be possible to make it work, he pointed out, but would take some effort.

A version of this article first appeared on Medscape.com.

An electronic nudge explaining the cardiovascular benefits of the influenza vaccine increased vaccination rates, particularly among people who had previously had a heart attack, showed the NUDGE FLU series of clinical trials.

Influenza has the potential to be a dangerous infection on its own, but it increases the risk for cardiovascular events among people with a history of heart attack, said the study’s lead author, Ankeet Bhatt, MD, a cardiologist at Kaiser Permanente San Francisco Medical Center, San Francisco.

“Yearly influenza vaccines help prevent influenza infection and, in patients with a heart attack, are potentially cardioprotective,” he said during his presentation at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago. The NUDGE FLU results were simultaneously published online in JAMA Cardiology.

In Denmark, where the trials were conducted, about 80% of older adults get flu shots, but only about 40% of younger adults with chronic diseases do, Bhatt reported. In the United States, about 45% of adults and 55% of children received at least one dose of the flu vaccine in the 2023/24 flu season, according to the US Centers for Disease Control and Prevention (CDC).

 

The NUDGE FLU Trials

Bhatt and his colleagues conducted three related clinical trials during the 2022/23 and 2023/24 flu seasons: NUDGE-FLU and NUDGE-FLU-2 targeted older adults, whereas NUDGE-FLU-CHRONIC targeted younger adults with chronic diseases. Nearly 2 million people were involved in the three trials.

Participants were randomized to receive one of a series of different behavioral-science-informed letters, delivered through a government-run electronic communication system, or no reminder.

People who received any of the nudges had higher rates of vaccination; among heart attack survivors, there was a 1.8% improvement and among adults without a history of heart attack, there was a 1.3% improvement. But a nudge that explained the potential cardiovascular benefits of flu shots was even more effective, leading to a 3.9% increase among people with a history of heart attack and a 2% increase among those with no heart attack history.

“A simple sentence resulted in a durable improvement in the vaccination rate,” said Bhatt.

The effect was even greater among those who had not been vaccinated in the previous flu season. Among heart attack survivors, nearly 14% more people got the vaccine compared with just 1.5% more survivors who were previously vaccinated. And it was most effective among younger adults who had experienced a recent heart attack, resulting in a 26% increase.

“The impact was larger in patients with a history of acute myocardial infarction, in those who were vaccine-hesitant, and in younger people” — all groups with the most to gain from vaccination in terms of cardiovascular protection — Bhatt reported.

About 25% of people in the United States are unsure about whether to get a flu shot, said Orly Vardeny, PharmD, professor of medicine at the University of Minnesota Medical School in Minneapolis, who was not involved in the study. The fact that previously unvaccinated people were convinced by the nudges is reassuring. “That’s the group where this intervention is most likely to move the needle,” she said.

Around half of all people hospitalized for flu in the United States have cardiovascular disease, CDC data showed, so “even a small increase in the number of patients who get vaccinated has substantial public health benefits,” Vardeny said.

The NUDGE FLU series showed that nudges like this should be employed as a simple tool to improve vaccination rates, but the system would be much more difficult to implement in the United States, Bhatt said.

Denmark has a national health service and a preexisting government electronic communication system, whereas the US system is privately run and more fractured. It would be possible to make it work, he pointed out, but would take some effort.

A version of this article first appeared on Medscape.com.

An electronic nudge explaining the cardiovascular benefits of the influenza vaccine increased vaccination rates, particularly among people who had previously had a heart attack, showed the NUDGE FLU series of clinical trials.

Influenza has the potential to be a dangerous infection on its own, but it increases the risk for cardiovascular events among people with a history of heart attack, said the study’s lead author, Ankeet Bhatt, MD, a cardiologist at Kaiser Permanente San Francisco Medical Center, San Francisco.

“Yearly influenza vaccines help prevent influenza infection and, in patients with a heart attack, are potentially cardioprotective,” he said during his presentation at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago. The NUDGE FLU results were simultaneously published online in JAMA Cardiology.

In Denmark, where the trials were conducted, about 80% of older adults get flu shots, but only about 40% of younger adults with chronic diseases do, Bhatt reported. In the United States, about 45% of adults and 55% of children received at least one dose of the flu vaccine in the 2023/24 flu season, according to the US Centers for Disease Control and Prevention (CDC).

 

The NUDGE FLU Trials

Bhatt and his colleagues conducted three related clinical trials during the 2022/23 and 2023/24 flu seasons: NUDGE-FLU and NUDGE-FLU-2 targeted older adults, whereas NUDGE-FLU-CHRONIC targeted younger adults with chronic diseases. Nearly 2 million people were involved in the three trials.

Participants were randomized to receive one of a series of different behavioral-science-informed letters, delivered through a government-run electronic communication system, or no reminder.

People who received any of the nudges had higher rates of vaccination; among heart attack survivors, there was a 1.8% improvement and among adults without a history of heart attack, there was a 1.3% improvement. But a nudge that explained the potential cardiovascular benefits of flu shots was even more effective, leading to a 3.9% increase among people with a history of heart attack and a 2% increase among those with no heart attack history.

“A simple sentence resulted in a durable improvement in the vaccination rate,” said Bhatt.

The effect was even greater among those who had not been vaccinated in the previous flu season. Among heart attack survivors, nearly 14% more people got the vaccine compared with just 1.5% more survivors who were previously vaccinated. And it was most effective among younger adults who had experienced a recent heart attack, resulting in a 26% increase.

“The impact was larger in patients with a history of acute myocardial infarction, in those who were vaccine-hesitant, and in younger people” — all groups with the most to gain from vaccination in terms of cardiovascular protection — Bhatt reported.

About 25% of people in the United States are unsure about whether to get a flu shot, said Orly Vardeny, PharmD, professor of medicine at the University of Minnesota Medical School in Minneapolis, who was not involved in the study. The fact that previously unvaccinated people were convinced by the nudges is reassuring. “That’s the group where this intervention is most likely to move the needle,” she said.

Around half of all people hospitalized for flu in the United States have cardiovascular disease, CDC data showed, so “even a small increase in the number of patients who get vaccinated has substantial public health benefits,” Vardeny said.

The NUDGE FLU series showed that nudges like this should be employed as a simple tool to improve vaccination rates, but the system would be much more difficult to implement in the United States, Bhatt said.

Denmark has a national health service and a preexisting government electronic communication system, whereas the US system is privately run and more fractured. It would be possible to make it work, he pointed out, but would take some effort.

A version of this article first appeared on Medscape.com.

Vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) offer important protection against severe illness for pregnant people and their babies.¹ However, vaccination coverage estimates among pregnant people remain suboptimal.^2-5 Additionally, some measures indicate that vaccine hesitancy among pregnant people is increasing; for example, 17.5% of surveyed pregnant women reported being very hesitant about influenza vaccination during pregnancy in 2019-2020, compared with 24.7% in 2022-2023.⁶As fall and winter virus season continues, consider opportunities for you and your staff to help communicate the importance of prenatal vaccination to pregnant patients in your care. Explore updated provider toolkits and prenatal vaccination patient education resources, including fact sheets, social media assets, posters, and short videos on respiratory syncytial virus (RSV), Tdap, COVID-19, influenza, and hepatitis B.

In an interview, CDC’s Haben Debessai, MD, an adjunct instructor in obstetrics and gynecology at Emory School of Medicine, Atlanta, Georgia, contextualizes the data to help healthcare professionals communicate effectively with their pregnant patients. 

 

What can practitioners communicate to patients about why it is important to get vaccinated during their pregnancy?

When communicating with their patients, practitioners can consider opportunities to discuss how vaccines work during pregnancy, emphasizing that prenatal vaccinations are beneficial for both the pregnant person and the fetus. It can be helpful to educate patients on how a pregnant person’s immune system can develop antibodies that will then pass to the fetus during the pregnancy and confer protection during the infant’s early months of life — when they are highly susceptible to illnesses that can be severe, such as RSV-associated lower respiratory tract infections. It can also be useful to discuss pregnancy’s impact on the immune system, which contributes to pregnant people being at higher risk for severe illness from infections like COVID-19 and flu, if contracted. The outcomes of severe illness can be dire for both the pregnant person and their pregnancy, which is why vaccination is the best mitigation option. It can also be beneficial to share with patients that some vaccines, like RSV and Tdap, are specifically for neonatal benefit, which could help patients understand why some vaccines are recommended at a specific gestational age and in each pregnancy or subsequent pregnancies. 

What is known about pregnant populations that experience disparities in vaccination coverage? 

While vaccination coverage among pregnant people is suboptimal, coverage estimates are often lowest among Black pregnant people, some of whom report experiencing mistreatment and discrimination during pregnancy and delivery.⁷ It is important to recognize that there are many intersecting factors that may impact vaccination coverage. Systemic and structural factors may prohibit some patient populations from accessing vaccinations (eg, transportation barriers, difficulty accessing adequate healthcare for those on government assistance, language barriers). To be responsive to the intersectional lived realities of each of these communities, the medical and public health community continually strives to increase trustworthiness, which can lead to increased uptake of vaccinations in these populations. 

What vaccines are available and recommended for pregnant people?

Four vaccines are routinely recommended during pregnancy: Tdap, COVID-19, influenza (seasonal), and RSV (seasonal). CDC recommends getting a Tdap vaccine between the 27th and 36th week of each pregnancy, preferably during the earlier part of this time period. CDC recommends that everyone 6 months or older in the United States, including pregnant people, stay up to date on COVID-19 vaccines. A COVID-19 vaccine can be given during any trimester of pregnancy. CDC recommends an annual flu vaccine during each flu season (fall/winter) for everyone 6 months or older in the United States, including pregnant people. A flu vaccine can be given during any trimester of pregnancy. For individuals who will be between 32 and 36 weeks pregnant during September through January, CDC recommends getting an RSV vaccine. RSV season and timing of vaccination may vary depending on geography. If a pregnant patient does not get the RSV vaccine during their pregnancy, CDC recommends that their baby receive an RSV monoclonal antibody (nirsevimab) to provide additional protection during the infant’s first RSV season, if they are younger than 8 months. At this time, pregnant people who received an RSV vaccine during a previous pregnancy (last year) are not recommended to receive another RSV vaccine during pregnancy. The current recommendation is for babies born during subsequent pregnancies to receive nirsevimab. Some pregnant people may also need other vaccines, such as hepatitis B. 

How can practitioners approach conversations about vaccination during pregnancy amid increasing vaccine hesitancy?

Many pregnant people who do get vaccinated describe their provider’s recommendation as an important motivator toward vaccination.^8-11 Communications research suggests that practitioners can further increase trustworthiness by openly discussing potential side effects of prenatal vaccinations and providing patients with a rationale for why each vaccine is recommended. Practitioners can also utilize opportunities to communicate that the risk for severe illness from whooping cough, COVID-19, flu, and RSV in pregnancy and among neonates in the first few months of life is often higher than the risk for an adverse reaction from receiving ACIP-recommended vaccines. Finally, practitioners can consider sharing tested and refined patient education resources at least one appointment prior to the recommended administration of each vaccine, providing individuals with time to process the information they need to facilitate their vaccine decision-making process.

Some patients may be more comfortable with older, well-known prenatal vaccinations but have skepticism about newer vaccines like COVID-19 and RSV. How can practitioners respond to these concerns?

As pregnant people navigate the challenges of making health decisions that could impact their developing baby, practitioners can build trust through empathetically responding to safety concerns and questions, particularly with respect to newly authorized vaccines. Vaccine confidence may be strengthened by communicating to patients that all recommended vaccinations, including those that have been newly authorized, have been rigorously tested prior to being recommended for pregnant people. Additionally, in my clinical practice, I see that patients are often more comfortable accepting vaccines when the benefit for the baby is clearly communicated. I have been pleasantly surprised that most patients I have counseled on the new maternal RSV vaccine have been receptive, making statements like, “If this will help protect my baby from getting sick, then yes, I will get it.”

As you and your staff care for pregnant patients during fall and winter virus season, remember that a provider recommendation remains one of the strongest known predictors of vaccination uptake.¹² As a trusted source of information about prenatal vaccination, consider further incorporating patient education resources to help communicate how prenatal vaccination helps pregnant people share important protection against severe illnesses with their babies. 

Haben Debessai, MD, is a Gilstrap Fellow at the CDC Foundation. Debessai also serves as an Emory Obstetrics/Gynecology Adjunct Instructor at Grady Health System in Atlanta, Georgia. She disclosed no relevant conflicts of interest.

References

1. ACOG Committee Opinion No. 741: Maternal Immunization. Obstet Gynecol. 2018;131:e214-e217. doi:10.1097/AOG.0000000000002662

2. Centers for Disease Control and Prevention. Flu, Tdap, and COVID-19 vaccination coverage among pregnant women – United States, April 2024. 2024 Sep 23. 3. Centers for Disease Control and Prevention. Respiratory syncytial virus (rsv) vaccination coverage, pregnant persons. 2024 Nov 19. 4. Centers for Disease Control and Prevention. COVID-19 vaccination coverage, pregnant persons. 2024 Nov 19. 5. Centers for Disease Control and Prevention. Influenza vaccination coverage, pregnant persons. 2024 Nov 19.6. Razzaghi H et al. IMMWR Morb Mortal Wkly Rep. 2023;72:1065-1071. Published 2023 Sep 29. doi: 10.15585/mmwr.mm7239a4

7. Mohamoud YA et al. MMWR Morb Mortal Wkly Rep 2023;72:961-967. doi: https://dx.doi.org/10.15585/mmwr.mm7235e1.

8. Kiefer MK et al. Am J Obstet Gynecol MFM. 2022;4:100603. doi: 10.1016/j.ajogmf.2022.100603

9. Spires B et al. Obstet Gynecol Clin North Am. 2023;50:401-419. doi: 10.1016/j.ogc.2023.02.013

10. Wales DP et al. Public Health. 2020;179:38-44. doi: 10.1016/j.puhe.2019.10.001

11. Zimmerman M et al. J Natl Med Assoc. 2023;115:362-376. doi:10.1016/j.jnma.2023.04.003

12. Castillo E et al. Best Pract Res Clin Obstet Gynaecol. 2021;76:83-95. doi:10.1016/j.bpobgyn.2021.03.008

Vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) offer important protection against severe illness for pregnant people and their babies.¹ However, vaccination coverage estimates among pregnant people remain suboptimal.^2-5 Additionally, some measures indicate that vaccine hesitancy among pregnant people is increasing; for example, 17.5% of surveyed pregnant women reported being very hesitant about influenza vaccination during pregnancy in 2019-2020, compared with 24.7% in 2022-2023.⁶As fall and winter virus season continues, consider opportunities for you and your staff to help communicate the importance of prenatal vaccination to pregnant patients in your care. Explore updated provider toolkits and prenatal vaccination patient education resources, including fact sheets, social media assets, posters, and short videos on respiratory syncytial virus (RSV), Tdap, COVID-19, influenza, and hepatitis B.

In an interview, CDC’s Haben Debessai, MD, an adjunct instructor in obstetrics and gynecology at Emory School of Medicine, Atlanta, Georgia, contextualizes the data to help healthcare professionals communicate effectively with their pregnant patients. 

 

What can practitioners communicate to patients about why it is important to get vaccinated during their pregnancy?

When communicating with their patients, practitioners can consider opportunities to discuss how vaccines work during pregnancy, emphasizing that prenatal vaccinations are beneficial for both the pregnant person and the fetus. It can be helpful to educate patients on how a pregnant person’s immune system can develop antibodies that will then pass to the fetus during the pregnancy and confer protection during the infant’s early months of life — when they are highly susceptible to illnesses that can be severe, such as RSV-associated lower respiratory tract infections. It can also be useful to discuss pregnancy’s impact on the immune system, which contributes to pregnant people being at higher risk for severe illness from infections like COVID-19 and flu, if contracted. The outcomes of severe illness can be dire for both the pregnant person and their pregnancy, which is why vaccination is the best mitigation option. It can also be beneficial to share with patients that some vaccines, like RSV and Tdap, are specifically for neonatal benefit, which could help patients understand why some vaccines are recommended at a specific gestational age and in each pregnancy or subsequent pregnancies. 

What is known about pregnant populations that experience disparities in vaccination coverage? 

While vaccination coverage among pregnant people is suboptimal, coverage estimates are often lowest among Black pregnant people, some of whom report experiencing mistreatment and discrimination during pregnancy and delivery.⁷ It is important to recognize that there are many intersecting factors that may impact vaccination coverage. Systemic and structural factors may prohibit some patient populations from accessing vaccinations (eg, transportation barriers, difficulty accessing adequate healthcare for those on government assistance, language barriers). To be responsive to the intersectional lived realities of each of these communities, the medical and public health community continually strives to increase trustworthiness, which can lead to increased uptake of vaccinations in these populations. 

What vaccines are available and recommended for pregnant people?

Four vaccines are routinely recommended during pregnancy: Tdap, COVID-19, influenza (seasonal), and RSV (seasonal). CDC recommends getting a Tdap vaccine between the 27th and 36th week of each pregnancy, preferably during the earlier part of this time period. CDC recommends that everyone 6 months or older in the United States, including pregnant people, stay up to date on COVID-19 vaccines. A COVID-19 vaccine can be given during any trimester of pregnancy. CDC recommends an annual flu vaccine during each flu season (fall/winter) for everyone 6 months or older in the United States, including pregnant people. A flu vaccine can be given during any trimester of pregnancy. For individuals who will be between 32 and 36 weeks pregnant during September through January, CDC recommends getting an RSV vaccine. RSV season and timing of vaccination may vary depending on geography. If a pregnant patient does not get the RSV vaccine during their pregnancy, CDC recommends that their baby receive an RSV monoclonal antibody (nirsevimab) to provide additional protection during the infant’s first RSV season, if they are younger than 8 months. At this time, pregnant people who received an RSV vaccine during a previous pregnancy (last year) are not recommended to receive another RSV vaccine during pregnancy. The current recommendation is for babies born during subsequent pregnancies to receive nirsevimab. Some pregnant people may also need other vaccines, such as hepatitis B. 

How can practitioners approach conversations about vaccination during pregnancy amid increasing vaccine hesitancy?

Many pregnant people who do get vaccinated describe their provider’s recommendation as an important motivator toward vaccination.^8-11 Communications research suggests that practitioners can further increase trustworthiness by openly discussing potential side effects of prenatal vaccinations and providing patients with a rationale for why each vaccine is recommended. Practitioners can also utilize opportunities to communicate that the risk for severe illness from whooping cough, COVID-19, flu, and RSV in pregnancy and among neonates in the first few months of life is often higher than the risk for an adverse reaction from receiving ACIP-recommended vaccines. Finally, practitioners can consider sharing tested and refined patient education resources at least one appointment prior to the recommended administration of each vaccine, providing individuals with time to process the information they need to facilitate their vaccine decision-making process.

Some patients may be more comfortable with older, well-known prenatal vaccinations but have skepticism about newer vaccines like COVID-19 and RSV. How can practitioners respond to these concerns?

As pregnant people navigate the challenges of making health decisions that could impact their developing baby, practitioners can build trust through empathetically responding to safety concerns and questions, particularly with respect to newly authorized vaccines. Vaccine confidence may be strengthened by communicating to patients that all recommended vaccinations, including those that have been newly authorized, have been rigorously tested prior to being recommended for pregnant people. Additionally, in my clinical practice, I see that patients are often more comfortable accepting vaccines when the benefit for the baby is clearly communicated. I have been pleasantly surprised that most patients I have counseled on the new maternal RSV vaccine have been receptive, making statements like, “If this will help protect my baby from getting sick, then yes, I will get it.”

As you and your staff care for pregnant patients during fall and winter virus season, remember that a provider recommendation remains one of the strongest known predictors of vaccination uptake.¹² As a trusted source of information about prenatal vaccination, consider further incorporating patient education resources to help communicate how prenatal vaccination helps pregnant people share important protection against severe illnesses with their babies. 

Haben Debessai, MD, is a Gilstrap Fellow at the CDC Foundation. Debessai also serves as an Emory Obstetrics/Gynecology Adjunct Instructor at Grady Health System in Atlanta, Georgia. She disclosed no relevant conflicts of interest.

References

1. ACOG Committee Opinion No. 741: Maternal Immunization. Obstet Gynecol. 2018;131:e214-e217. doi:10.1097/AOG.0000000000002662

2. Centers for Disease Control and Prevention. Flu, Tdap, and COVID-19 vaccination coverage among pregnant women – United States, April 2024. 2024 Sep 23. 3. Centers for Disease Control and Prevention. Respiratory syncytial virus (rsv) vaccination coverage, pregnant persons. 2024 Nov 19. 4. Centers for Disease Control and Prevention. COVID-19 vaccination coverage, pregnant persons. 2024 Nov 19. 5. Centers for Disease Control and Prevention. Influenza vaccination coverage, pregnant persons. 2024 Nov 19.6. Razzaghi H et al. IMMWR Morb Mortal Wkly Rep. 2023;72:1065-1071. Published 2023 Sep 29. doi: 10.15585/mmwr.mm7239a4

7. Mohamoud YA et al. MMWR Morb Mortal Wkly Rep 2023;72:961-967. doi: https://dx.doi.org/10.15585/mmwr.mm7235e1.

8. Kiefer MK et al. Am J Obstet Gynecol MFM. 2022;4:100603. doi: 10.1016/j.ajogmf.2022.100603

9. Spires B et al. Obstet Gynecol Clin North Am. 2023;50:401-419. doi: 10.1016/j.ogc.2023.02.013

10. Wales DP et al. Public Health. 2020;179:38-44. doi: 10.1016/j.puhe.2019.10.001

11. Zimmerman M et al. J Natl Med Assoc. 2023;115:362-376. doi:10.1016/j.jnma.2023.04.003

12. Castillo E et al. Best Pract Res Clin Obstet Gynaecol. 2021;76:83-95. doi:10.1016/j.bpobgyn.2021.03.008

Vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) offer important protection against severe illness for pregnant people and their babies.¹ However, vaccination coverage estimates among pregnant people remain suboptimal.^2-5 Additionally, some measures indicate that vaccine hesitancy among pregnant people is increasing; for example, 17.5% of surveyed pregnant women reported being very hesitant about influenza vaccination during pregnancy in 2019-2020, compared with 24.7% in 2022-2023.⁶As fall and winter virus season continues, consider opportunities for you and your staff to help communicate the importance of prenatal vaccination to pregnant patients in your care. Explore updated provider toolkits and prenatal vaccination patient education resources, including fact sheets, social media assets, posters, and short videos on respiratory syncytial virus (RSV), Tdap, COVID-19, influenza, and hepatitis B.

In an interview, CDC’s Haben Debessai, MD, an adjunct instructor in obstetrics and gynecology at Emory School of Medicine, Atlanta, Georgia, contextualizes the data to help healthcare professionals communicate effectively with their pregnant patients. 

 

What can practitioners communicate to patients about why it is important to get vaccinated during their pregnancy?

When communicating with their patients, practitioners can consider opportunities to discuss how vaccines work during pregnancy, emphasizing that prenatal vaccinations are beneficial for both the pregnant person and the fetus. It can be helpful to educate patients on how a pregnant person’s immune system can develop antibodies that will then pass to the fetus during the pregnancy and confer protection during the infant’s early months of life — when they are highly susceptible to illnesses that can be severe, such as RSV-associated lower respiratory tract infections. It can also be useful to discuss pregnancy’s impact on the immune system, which contributes to pregnant people being at higher risk for severe illness from infections like COVID-19 and flu, if contracted. The outcomes of severe illness can be dire for both the pregnant person and their pregnancy, which is why vaccination is the best mitigation option. It can also be beneficial to share with patients that some vaccines, like RSV and Tdap, are specifically for neonatal benefit, which could help patients understand why some vaccines are recommended at a specific gestational age and in each pregnancy or subsequent pregnancies. 

What is known about pregnant populations that experience disparities in vaccination coverage? 

While vaccination coverage among pregnant people is suboptimal, coverage estimates are often lowest among Black pregnant people, some of whom report experiencing mistreatment and discrimination during pregnancy and delivery.⁷ It is important to recognize that there are many intersecting factors that may impact vaccination coverage. Systemic and structural factors may prohibit some patient populations from accessing vaccinations (eg, transportation barriers, difficulty accessing adequate healthcare for those on government assistance, language barriers). To be responsive to the intersectional lived realities of each of these communities, the medical and public health community continually strives to increase trustworthiness, which can lead to increased uptake of vaccinations in these populations. 

What vaccines are available and recommended for pregnant people?

Four vaccines are routinely recommended during pregnancy: Tdap, COVID-19, influenza (seasonal), and RSV (seasonal). CDC recommends getting a Tdap vaccine between the 27th and 36th week of each pregnancy, preferably during the earlier part of this time period. CDC recommends that everyone 6 months or older in the United States, including pregnant people, stay up to date on COVID-19 vaccines. A COVID-19 vaccine can be given during any trimester of pregnancy. CDC recommends an annual flu vaccine during each flu season (fall/winter) for everyone 6 months or older in the United States, including pregnant people. A flu vaccine can be given during any trimester of pregnancy. For individuals who will be between 32 and 36 weeks pregnant during September through January, CDC recommends getting an RSV vaccine. RSV season and timing of vaccination may vary depending on geography. If a pregnant patient does not get the RSV vaccine during their pregnancy, CDC recommends that their baby receive an RSV monoclonal antibody (nirsevimab) to provide additional protection during the infant’s first RSV season, if they are younger than 8 months. At this time, pregnant people who received an RSV vaccine during a previous pregnancy (last year) are not recommended to receive another RSV vaccine during pregnancy. The current recommendation is for babies born during subsequent pregnancies to receive nirsevimab. Some pregnant people may also need other vaccines, such as hepatitis B. 

How can practitioners approach conversations about vaccination during pregnancy amid increasing vaccine hesitancy?

Many pregnant people who do get vaccinated describe their provider’s recommendation as an important motivator toward vaccination.^8-11 Communications research suggests that practitioners can further increase trustworthiness by openly discussing potential side effects of prenatal vaccinations and providing patients with a rationale for why each vaccine is recommended. Practitioners can also utilize opportunities to communicate that the risk for severe illness from whooping cough, COVID-19, flu, and RSV in pregnancy and among neonates in the first few months of life is often higher than the risk for an adverse reaction from receiving ACIP-recommended vaccines. Finally, practitioners can consider sharing tested and refined patient education resources at least one appointment prior to the recommended administration of each vaccine, providing individuals with time to process the information they need to facilitate their vaccine decision-making process.

Some patients may be more comfortable with older, well-known prenatal vaccinations but have skepticism about newer vaccines like COVID-19 and RSV. How can practitioners respond to these concerns?

As pregnant people navigate the challenges of making health decisions that could impact their developing baby, practitioners can build trust through empathetically responding to safety concerns and questions, particularly with respect to newly authorized vaccines. Vaccine confidence may be strengthened by communicating to patients that all recommended vaccinations, including those that have been newly authorized, have been rigorously tested prior to being recommended for pregnant people. Additionally, in my clinical practice, I see that patients are often more comfortable accepting vaccines when the benefit for the baby is clearly communicated. I have been pleasantly surprised that most patients I have counseled on the new maternal RSV vaccine have been receptive, making statements like, “If this will help protect my baby from getting sick, then yes, I will get it.”

As you and your staff care for pregnant patients during fall and winter virus season, remember that a provider recommendation remains one of the strongest known predictors of vaccination uptake.¹² As a trusted source of information about prenatal vaccination, consider further incorporating patient education resources to help communicate how prenatal vaccination helps pregnant people share important protection against severe illnesses with their babies. 

Haben Debessai, MD, is a Gilstrap Fellow at the CDC Foundation. Debessai also serves as an Emory Obstetrics/Gynecology Adjunct Instructor at Grady Health System in Atlanta, Georgia. She disclosed no relevant conflicts of interest.

References

1. ACOG Committee Opinion No. 741: Maternal Immunization. Obstet Gynecol. 2018;131:e214-e217. doi:10.1097/AOG.0000000000002662

2. Centers for Disease Control and Prevention. Flu, Tdap, and COVID-19 vaccination coverage among pregnant women – United States, April 2024. 2024 Sep 23. 3. Centers for Disease Control and Prevention. Respiratory syncytial virus (rsv) vaccination coverage, pregnant persons. 2024 Nov 19. 4. Centers for Disease Control and Prevention. COVID-19 vaccination coverage, pregnant persons. 2024 Nov 19. 5. Centers for Disease Control and Prevention. Influenza vaccination coverage, pregnant persons. 2024 Nov 19.6. Razzaghi H et al. IMMWR Morb Mortal Wkly Rep. 2023;72:1065-1071. Published 2023 Sep 29. doi: 10.15585/mmwr.mm7239a4

7. Mohamoud YA et al. MMWR Morb Mortal Wkly Rep 2023;72:961-967. doi: https://dx.doi.org/10.15585/mmwr.mm7235e1.

8. Kiefer MK et al. Am J Obstet Gynecol MFM. 2022;4:100603. doi: 10.1016/j.ajogmf.2022.100603

9. Spires B et al. Obstet Gynecol Clin North Am. 2023;50:401-419. doi: 10.1016/j.ogc.2023.02.013

10. Wales DP et al. Public Health. 2020;179:38-44. doi: 10.1016/j.puhe.2019.10.001

11. Zimmerman M et al. J Natl Med Assoc. 2023;115:362-376. doi:10.1016/j.jnma.2023.04.003

12. Castillo E et al. Best Pract Res Clin Obstet Gynaecol. 2021;76:83-95. doi:10.1016/j.bpobgyn.2021.03.008

TOPLINE:

In patients with stage II or III colorectal cancer (CRC), frequent follow-up testing with CT scans and serum carcinoembryonic antigen (CEA) screening provides no significant overall or cancer-specific survival benefits at 10 years, according to findings from a secondary analysis.

METHODOLOGY:

• After curative surgery for CRC, intensive patient follow-up is common in clinical practice. However, there’s limited evidence to suggest that more frequent testing provides a long-term survival benefit.
• In the COLOFOL trial, patients with stage II or III CRC who had undergone curative resection were randomly assigned to either high-frequency follow-up (CT scans and CEA screening at 6, 12, 18, 24, and 36 months) or low-frequency follow-up (testing at 12 and 36 months) after surgery.
• This secondary analysis of the COLOFOL trial included 2456 patients (median age, 65 years), 1227 of whom received high-frequency follow-up and 1229 of whom received low-frequency follow-up.
• The main outcome of the secondary analysis was 10-year overall mortality and CRC–specific mortality rates.
• The analysis included both intention-to-treat and per-protocol approaches, with outcomes measured through December 2020.

TAKEAWAY:

• In the intention-to-treat analysis, the 10-year overall mortality rates were similar between the high- and low-frequency follow-up groups — 27.1% and 28.4%, respectively (risk difference, 1.3%; P = .46).
• A per-protocol analysis confirmed these findings: The 10-year overall mortality risk was 26.4% in the high-frequency group and 27.8% in the low-frequency group.
• The 10-year CRC–specific mortality rate was also similar between the high-frequency and low-frequency groups — 15.6% and 16.0%, respectively — (risk difference, 0.4%; P = .72). The same pattern was seen in the per-protocol analysis, which found a 10-year CRC–specific mortality risk of 15.6% in the high-frequency group and 15.9% in the low-frequency group.
• Subgroup analyses by cancer stage and location (rectal and colon) also revealed no significant differences in mortality outcomes between the two follow-up groups.

IN PRACTICE:

“This secondary analysis of the COLOFOL randomized clinical trial found that, among patients with stage II or III colorectal cancer, more frequent follow-up testing with CT scan and CEA screening, compared with less frequent follow-up, did not result in a significant rate reduction in 10-year overall mortality or colorectal cancer-specific mortality,” the authors concluded. “The results of this trial should be considered as the evidence base for updating clinical guidelines.”

SOURCE:

The study, led by Henrik Toft Sørensen, MD, PhD, DMSc, DSc, Aarhus University Hospital and Aarhus University, Aarhus, Denmark, was published online in JAMA Network Open.

LIMITATIONS:

The staff turnover at recruitment centers potentially affected protocol adherence. The inability to blind patients and physicians to the follow-up frequency was another limitation. The low-frequency follow-up protocol was less intensive than that recommended in the current guidelines by the National Comprehensive Cancer Network and the American Society of Clinical Oncology, potentially limiting comparisons to current standard practices.

DISCLOSURES:

The initial trial received unrestricted grants from multiple organizations including the Nordic Cancer Union, A.P. Møller Foundation, Beckett Foundation, Danish Cancer Society, and Swedish Cancer Foundation project. The authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

In patients with stage II or III colorectal cancer (CRC), frequent follow-up testing with CT scans and serum carcinoembryonic antigen (CEA) screening provides no significant overall or cancer-specific survival benefits at 10 years, according to findings from a secondary analysis.

METHODOLOGY:

• After curative surgery for CRC, intensive patient follow-up is common in clinical practice. However, there’s limited evidence to suggest that more frequent testing provides a long-term survival benefit.
• In the COLOFOL trial, patients with stage II or III CRC who had undergone curative resection were randomly assigned to either high-frequency follow-up (CT scans and CEA screening at 6, 12, 18, 24, and 36 months) or low-frequency follow-up (testing at 12 and 36 months) after surgery.
• This secondary analysis of the COLOFOL trial included 2456 patients (median age, 65 years), 1227 of whom received high-frequency follow-up and 1229 of whom received low-frequency follow-up.
• The main outcome of the secondary analysis was 10-year overall mortality and CRC–specific mortality rates.
• The analysis included both intention-to-treat and per-protocol approaches, with outcomes measured through December 2020.

TAKEAWAY:

• In the intention-to-treat analysis, the 10-year overall mortality rates were similar between the high- and low-frequency follow-up groups — 27.1% and 28.4%, respectively (risk difference, 1.3%; P = .46).
• A per-protocol analysis confirmed these findings: The 10-year overall mortality risk was 26.4% in the high-frequency group and 27.8% in the low-frequency group.
• The 10-year CRC–specific mortality rate was also similar between the high-frequency and low-frequency groups — 15.6% and 16.0%, respectively — (risk difference, 0.4%; P = .72). The same pattern was seen in the per-protocol analysis, which found a 10-year CRC–specific mortality risk of 15.6% in the high-frequency group and 15.9% in the low-frequency group.
• Subgroup analyses by cancer stage and location (rectal and colon) also revealed no significant differences in mortality outcomes between the two follow-up groups.

IN PRACTICE:

“This secondary analysis of the COLOFOL randomized clinical trial found that, among patients with stage II or III colorectal cancer, more frequent follow-up testing with CT scan and CEA screening, compared with less frequent follow-up, did not result in a significant rate reduction in 10-year overall mortality or colorectal cancer-specific mortality,” the authors concluded. “The results of this trial should be considered as the evidence base for updating clinical guidelines.”

SOURCE:

The study, led by Henrik Toft Sørensen, MD, PhD, DMSc, DSc, Aarhus University Hospital and Aarhus University, Aarhus, Denmark, was published online in JAMA Network Open.

LIMITATIONS:

The staff turnover at recruitment centers potentially affected protocol adherence. The inability to blind patients and physicians to the follow-up frequency was another limitation. The low-frequency follow-up protocol was less intensive than that recommended in the current guidelines by the National Comprehensive Cancer Network and the American Society of Clinical Oncology, potentially limiting comparisons to current standard practices.

DISCLOSURES:

The initial trial received unrestricted grants from multiple organizations including the Nordic Cancer Union, A.P. Møller Foundation, Beckett Foundation, Danish Cancer Society, and Swedish Cancer Foundation project. The authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

In patients with stage II or III colorectal cancer (CRC), frequent follow-up testing with CT scans and serum carcinoembryonic antigen (CEA) screening provides no significant overall or cancer-specific survival benefits at 10 years, according to findings from a secondary analysis.

METHODOLOGY:

• After curative surgery for CRC, intensive patient follow-up is common in clinical practice. However, there’s limited evidence to suggest that more frequent testing provides a long-term survival benefit.
• In the COLOFOL trial, patients with stage II or III CRC who had undergone curative resection were randomly assigned to either high-frequency follow-up (CT scans and CEA screening at 6, 12, 18, 24, and 36 months) or low-frequency follow-up (testing at 12 and 36 months) after surgery.
• This secondary analysis of the COLOFOL trial included 2456 patients (median age, 65 years), 1227 of whom received high-frequency follow-up and 1229 of whom received low-frequency follow-up.
• The main outcome of the secondary analysis was 10-year overall mortality and CRC–specific mortality rates.
• The analysis included both intention-to-treat and per-protocol approaches, with outcomes measured through December 2020.

TAKEAWAY:

• In the intention-to-treat analysis, the 10-year overall mortality rates were similar between the high- and low-frequency follow-up groups — 27.1% and 28.4%, respectively (risk difference, 1.3%; P = .46).
• A per-protocol analysis confirmed these findings: The 10-year overall mortality risk was 26.4% in the high-frequency group and 27.8% in the low-frequency group.
• The 10-year CRC–specific mortality rate was also similar between the high-frequency and low-frequency groups — 15.6% and 16.0%, respectively — (risk difference, 0.4%; P = .72). The same pattern was seen in the per-protocol analysis, which found a 10-year CRC–specific mortality risk of 15.6% in the high-frequency group and 15.9% in the low-frequency group.
• Subgroup analyses by cancer stage and location (rectal and colon) also revealed no significant differences in mortality outcomes between the two follow-up groups.

IN PRACTICE:

“This secondary analysis of the COLOFOL randomized clinical trial found that, among patients with stage II or III colorectal cancer, more frequent follow-up testing with CT scan and CEA screening, compared with less frequent follow-up, did not result in a significant rate reduction in 10-year overall mortality or colorectal cancer-specific mortality,” the authors concluded. “The results of this trial should be considered as the evidence base for updating clinical guidelines.”

SOURCE:

The study, led by Henrik Toft Sørensen, MD, PhD, DMSc, DSc, Aarhus University Hospital and Aarhus University, Aarhus, Denmark, was published online in JAMA Network Open.

LIMITATIONS:

The staff turnover at recruitment centers potentially affected protocol adherence. The inability to blind patients and physicians to the follow-up frequency was another limitation. The low-frequency follow-up protocol was less intensive than that recommended in the current guidelines by the National Comprehensive Cancer Network and the American Society of Clinical Oncology, potentially limiting comparisons to current standard practices.

DISCLOSURES:

The initial trial received unrestricted grants from multiple organizations including the Nordic Cancer Union, A.P. Møller Foundation, Beckett Foundation, Danish Cancer Society, and Swedish Cancer Foundation project. The authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

The heart’s “mini-brain” is independent and highly localized, according to researchers at the Karolinska Institutet in Stockholm, Sweden. The findings could lead to new research into arrhythmia, dementia, and Parkinson’s disease.

Although controlled by the brain, the heart has a separate, smaller intracardiac nervous system (IcNS) embedded within the superficial layers of the heart wall. Nicknamed the mini-brain by researchers decades ago, the IcNS was assumed to be a simple structure capable only of relaying simple information from the brain to the heart.

The neurons in the mini-brain, however, have been under-researched, said Konstantinos Ampatzis, principal researcher and assistant professor of neuroscience at the Karolinska Institutet. “Cardiologists know that neurons exist but never study them because their first concern is the cardiac muscle cells, or cardiomyocytes, that are responsible for the heartbeat,” he explained. “Neuroscientists understand and decode neurons but don’t know about neurons in the heart.”

Ampatzis’s team mapped the exact composition, organization, and function of neurons in the IcNS using zebrafish as an animal model. “The heart of the zebrafish is closer to that of humans than the mouse heart is,” he explained. “The heart rate of a zebrafish is exactly the same.”

Several techniques were used to characterize these neurons. Electrophysiology determined their function, and researchers at Columbia University in New York City helped identify their molecular signatures using single-cell RNA sequencing. Ampatzis and his team also analyzed neurotransmitters that the neurons release to communicate with each other. Researchers in Sweden and New York worked on this project in their spare time because they had no additional funding.

Ampatzis expected to see ganglions or relay neurons capable only of receiving or sending information. “But we found a very diverse set of neurons in a small network,” he said. Their findings included sympathetic, parasympathetic, and sensory neurons with apparent neurochemical and functional diversity. Most surprising was a subset of pacemaker neurons. “You cannot have a network that produces a rhythm without these neurons, and we didn’t expect exactly that, to be honest,” he said.

Pacemaker neurons are usually associated with so-called central pattern generator networks within the central nervous system. These independent, highly localized neuronal networks generate and control complex rhythmic behaviors such as respiration, mastication, urination, and ejaculation. “Most importantly, we found that this neuronal network works in an isolated heart, without brain information, and can change the rhythm of the heart and the regularity by itself,” said Ampatzis.

Further studies confirmed that neurons do not produce the rhythm, which is controlled by the cardiomyocytes. The neurons’ main function is to regulate the speed of the heartbeat. In other words, this smaller localized network acts as a kind of insurance system to safeguard the brain’s control of the heartbeat. “From an evolutionary perspective, I think that the system is like this because the heartbeat defines life,” Ampatzis added.

With the neurons of the heart mapped, medical researchers now have a toolbox of molecular markers, neurotransmitters, and other information on how such neurons function. These findings could become the basis of new research. It might be possible to investigate heart arrhythmia by modulating pacemaker neurons, Ampatzis suggested. “You could even repurpose or find specific drugs that can interfere with this local network of the heart,” he said, adding that this might be a less invasive option than is possible today.

Arrhythmia affects millions of people, said Oliver Guttmann, MD, a consultant cardiologist at The Wellington Hospital and honorary associate professor of cardiology at University College London, both in London, England. Beta-blockers remain the drug of choice for arrhythmia, but other options can be invasive. “We do ablations to try and burn or freeze certain areas of the heart to get rid of a rhythm because often this comes from hyperactive cells somewhere,” he said. Pacemakers and defibrillators are also needed to modulate dangerous rhythms. Innovation is focusing on making interventions far less invasive than they are today by creating smaller and smaller pacemakers, for example.

Moving from zebrafish to more complex mammalian systems will be the next big step, said David Paterson, DPhil, head of the Department of Physiology, Anatomy, and Genetics and honorary director of Burdon Sanderson Cardiac Science Centre at the University of Oxford in England. “If you can find the molecular road map of dysregulation, then that could be a potential target for a gene therapy or cell therapy or for neuromodulation therapy,” he explained. Interest in this field, which is sometimes called bioelectronic medicine, is mounting. “It’s like pharmaceutics, but there’s no drug. You’re tapping into the wiring of the nervous system,” he added.

More radical research pathways might look at ways to tackle neurodegenerative disorders from dementia to Parkinson’s disease. “If neurons die in the brain, then they die in the heart and can affect the rhythm of the heart,” said Ampatzis. But zebrafish neurons are now known to produce substances that induce a proliferation of stem cells in bones, skin, and even the nervous system. “We think those neurons of the heart could perhaps contribute to the regeneration of the heart,” he said.

Ampatzis, Guttmann, and Paterson reported having no relevant financial relationships.

A version of this article appeared on Medscape.com.

The heart’s “mini-brain” is independent and highly localized, according to researchers at the Karolinska Institutet in Stockholm, Sweden. The findings could lead to new research into arrhythmia, dementia, and Parkinson’s disease.

Although controlled by the brain, the heart has a separate, smaller intracardiac nervous system (IcNS) embedded within the superficial layers of the heart wall. Nicknamed the mini-brain by researchers decades ago, the IcNS was assumed to be a simple structure capable only of relaying simple information from the brain to the heart.

The neurons in the mini-brain, however, have been under-researched, said Konstantinos Ampatzis, principal researcher and assistant professor of neuroscience at the Karolinska Institutet. “Cardiologists know that neurons exist but never study them because their first concern is the cardiac muscle cells, or cardiomyocytes, that are responsible for the heartbeat,” he explained. “Neuroscientists understand and decode neurons but don’t know about neurons in the heart.”

Ampatzis’s team mapped the exact composition, organization, and function of neurons in the IcNS using zebrafish as an animal model. “The heart of the zebrafish is closer to that of humans than the mouse heart is,” he explained. “The heart rate of a zebrafish is exactly the same.”

Several techniques were used to characterize these neurons. Electrophysiology determined their function, and researchers at Columbia University in New York City helped identify their molecular signatures using single-cell RNA sequencing. Ampatzis and his team also analyzed neurotransmitters that the neurons release to communicate with each other. Researchers in Sweden and New York worked on this project in their spare time because they had no additional funding.

Ampatzis expected to see ganglions or relay neurons capable only of receiving or sending information. “But we found a very diverse set of neurons in a small network,” he said. Their findings included sympathetic, parasympathetic, and sensory neurons with apparent neurochemical and functional diversity. Most surprising was a subset of pacemaker neurons. “You cannot have a network that produces a rhythm without these neurons, and we didn’t expect exactly that, to be honest,” he said.

Pacemaker neurons are usually associated with so-called central pattern generator networks within the central nervous system. These independent, highly localized neuronal networks generate and control complex rhythmic behaviors such as respiration, mastication, urination, and ejaculation. “Most importantly, we found that this neuronal network works in an isolated heart, without brain information, and can change the rhythm of the heart and the regularity by itself,” said Ampatzis.

Further studies confirmed that neurons do not produce the rhythm, which is controlled by the cardiomyocytes. The neurons’ main function is to regulate the speed of the heartbeat. In other words, this smaller localized network acts as a kind of insurance system to safeguard the brain’s control of the heartbeat. “From an evolutionary perspective, I think that the system is like this because the heartbeat defines life,” Ampatzis added.

With the neurons of the heart mapped, medical researchers now have a toolbox of molecular markers, neurotransmitters, and other information on how such neurons function. These findings could become the basis of new research. It might be possible to investigate heart arrhythmia by modulating pacemaker neurons, Ampatzis suggested. “You could even repurpose or find specific drugs that can interfere with this local network of the heart,” he said, adding that this might be a less invasive option than is possible today.

Arrhythmia affects millions of people, said Oliver Guttmann, MD, a consultant cardiologist at The Wellington Hospital and honorary associate professor of cardiology at University College London, both in London, England. Beta-blockers remain the drug of choice for arrhythmia, but other options can be invasive. “We do ablations to try and burn or freeze certain areas of the heart to get rid of a rhythm because often this comes from hyperactive cells somewhere,” he said. Pacemakers and defibrillators are also needed to modulate dangerous rhythms. Innovation is focusing on making interventions far less invasive than they are today by creating smaller and smaller pacemakers, for example.

Moving from zebrafish to more complex mammalian systems will be the next big step, said David Paterson, DPhil, head of the Department of Physiology, Anatomy, and Genetics and honorary director of Burdon Sanderson Cardiac Science Centre at the University of Oxford in England. “If you can find the molecular road map of dysregulation, then that could be a potential target for a gene therapy or cell therapy or for neuromodulation therapy,” he explained. Interest in this field, which is sometimes called bioelectronic medicine, is mounting. “It’s like pharmaceutics, but there’s no drug. You’re tapping into the wiring of the nervous system,” he added.

More radical research pathways might look at ways to tackle neurodegenerative disorders from dementia to Parkinson’s disease. “If neurons die in the brain, then they die in the heart and can affect the rhythm of the heart,” said Ampatzis. But zebrafish neurons are now known to produce substances that induce a proliferation of stem cells in bones, skin, and even the nervous system. “We think those neurons of the heart could perhaps contribute to the regeneration of the heart,” he said.

Ampatzis, Guttmann, and Paterson reported having no relevant financial relationships.

A version of this article appeared on Medscape.com.

The heart’s “mini-brain” is independent and highly localized, according to researchers at the Karolinska Institutet in Stockholm, Sweden. The findings could lead to new research into arrhythmia, dementia, and Parkinson’s disease.

Although controlled by the brain, the heart has a separate, smaller intracardiac nervous system (IcNS) embedded within the superficial layers of the heart wall. Nicknamed the mini-brain by researchers decades ago, the IcNS was assumed to be a simple structure capable only of relaying simple information from the brain to the heart.

The neurons in the mini-brain, however, have been under-researched, said Konstantinos Ampatzis, principal researcher and assistant professor of neuroscience at the Karolinska Institutet. “Cardiologists know that neurons exist but never study them because their first concern is the cardiac muscle cells, or cardiomyocytes, that are responsible for the heartbeat,” he explained. “Neuroscientists understand and decode neurons but don’t know about neurons in the heart.”

Ampatzis’s team mapped the exact composition, organization, and function of neurons in the IcNS using zebrafish as an animal model. “The heart of the zebrafish is closer to that of humans than the mouse heart is,” he explained. “The heart rate of a zebrafish is exactly the same.”

Several techniques were used to characterize these neurons. Electrophysiology determined their function, and researchers at Columbia University in New York City helped identify their molecular signatures using single-cell RNA sequencing. Ampatzis and his team also analyzed neurotransmitters that the neurons release to communicate with each other. Researchers in Sweden and New York worked on this project in their spare time because they had no additional funding.

Ampatzis expected to see ganglions or relay neurons capable only of receiving or sending information. “But we found a very diverse set of neurons in a small network,” he said. Their findings included sympathetic, parasympathetic, and sensory neurons with apparent neurochemical and functional diversity. Most surprising was a subset of pacemaker neurons. “You cannot have a network that produces a rhythm without these neurons, and we didn’t expect exactly that, to be honest,” he said.

Pacemaker neurons are usually associated with so-called central pattern generator networks within the central nervous system. These independent, highly localized neuronal networks generate and control complex rhythmic behaviors such as respiration, mastication, urination, and ejaculation. “Most importantly, we found that this neuronal network works in an isolated heart, without brain information, and can change the rhythm of the heart and the regularity by itself,” said Ampatzis.

Further studies confirmed that neurons do not produce the rhythm, which is controlled by the cardiomyocytes. The neurons’ main function is to regulate the speed of the heartbeat. In other words, this smaller localized network acts as a kind of insurance system to safeguard the brain’s control of the heartbeat. “From an evolutionary perspective, I think that the system is like this because the heartbeat defines life,” Ampatzis added.

With the neurons of the heart mapped, medical researchers now have a toolbox of molecular markers, neurotransmitters, and other information on how such neurons function. These findings could become the basis of new research. It might be possible to investigate heart arrhythmia by modulating pacemaker neurons, Ampatzis suggested. “You could even repurpose or find specific drugs that can interfere with this local network of the heart,” he said, adding that this might be a less invasive option than is possible today.

Arrhythmia affects millions of people, said Oliver Guttmann, MD, a consultant cardiologist at The Wellington Hospital and honorary associate professor of cardiology at University College London, both in London, England. Beta-blockers remain the drug of choice for arrhythmia, but other options can be invasive. “We do ablations to try and burn or freeze certain areas of the heart to get rid of a rhythm because often this comes from hyperactive cells somewhere,” he said. Pacemakers and defibrillators are also needed to modulate dangerous rhythms. Innovation is focusing on making interventions far less invasive than they are today by creating smaller and smaller pacemakers, for example.

Moving from zebrafish to more complex mammalian systems will be the next big step, said David Paterson, DPhil, head of the Department of Physiology, Anatomy, and Genetics and honorary director of Burdon Sanderson Cardiac Science Centre at the University of Oxford in England. “If you can find the molecular road map of dysregulation, then that could be a potential target for a gene therapy or cell therapy or for neuromodulation therapy,” he explained. Interest in this field, which is sometimes called bioelectronic medicine, is mounting. “It’s like pharmaceutics, but there’s no drug. You’re tapping into the wiring of the nervous system,” he added.

More radical research pathways might look at ways to tackle neurodegenerative disorders from dementia to Parkinson’s disease. “If neurons die in the brain, then they die in the heart and can affect the rhythm of the heart,” said Ampatzis. But zebrafish neurons are now known to produce substances that induce a proliferation of stem cells in bones, skin, and even the nervous system. “We think those neurons of the heart could perhaps contribute to the regeneration of the heart,” he said.

Ampatzis, Guttmann, and Paterson reported having no relevant financial relationships.

A version of this article appeared on Medscape.com.